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Diversification, Flexibility and Scale Position New Company
for Success in Dynamic Global Health Care Environment Establishes Leadership in Human, Animal, and Consumer Health,
including Primary and Specialty Care; in Vaccines, Biologics and Small
Molecules; and Across Developed and Emerging Markets Unique and Flexible Business Model Features Focus and
Agility of Smaller Enterprises Backed by Resources and Scale of Global Company Combination Strengthens Platform for Improved, Consistent,
and Stable Earnings Growth and Sustainable Shareholder Value New Company Will Promote Health and Wellness and Respond
More Effectively to Unmet Needs of Patients, Physicians, and Customers Around
the World NEW YORK, NY and MADISON, NJ--January 26, 2009 - Pfizer and
Wyeth announced that they have entered into a definitive merger agreement under
which Pfizer will acquire Wyeth in a cash-and-stock transaction currently
valued at $50.19 per share, or a total of approximately $68 billion. The Boards
of Directors of both companies have approved the combination. The combined company will create one of the most diversified
companies in the global health care industry. Operating through patient-centric
businesses that match the speed and agility of small, focused enterprises with
the benefits of a global organization's scale and resources, the company will
respond more quickly and effectively to meet changing health care needs. The
combined company will have product offerings in numerous growing therapeutic
areas, a strong product pipeline, leading scientific and manufacturing
capabilities, and a premier global footprint in health care. With its broad and diversified global product portfolio and
reduced dependence on small molecules, the new company will be positioned for
improved, consistent, and stable top-line and EPS growth and sustainable
shareholder value in the short and long term. It is expected that no drug will
account for more than 10 percent of the combined company's revenue in 2012. Financial Highlights Under the terms of the transaction, each outstanding share
of Wyeth common stock will be converted into the right to receive $33 in cash
and 0.985 of a share of Pfizer common stock, subject to the terms of the merger
agreement. Based on the closing price of Pfizer stock as of January 23, 2009,
the stock component is valued at $17.19 per share. The transaction provides
immediate value to Wyeth shareholders through the cash component, as well as
continued participation in the future prospects expected to result from the
combination through their ownership of approximately 16 percent of Pfizer's
shares. The deal is expected to be accretive to Pfizer's adjusted
diluted earnings per share in the second full year after closing(1). The
transaction is anticipated to yield cost savings of approximately $4 billion to
be fully realized by the third year after closing. Savings are expected in
selling, informational and administrative functions, research and development,
and manufacturing. The transaction will be financed through a combination of
cash, debt and stock. A consortium of banks has provided commitments for a
total of $22.5 billion in debt. In connection with the proposed transaction between Pfizer
and Wyeth, the Board of Directors of Pfizer has determined that, effective with
the dividend to be paid in the second quarter of 2009, it will reduce Pfizer's
quarterly dividend per share to $0.16, which continues to be competitive with
other industry participants. Pfizer believes the transaction offers significant
opportunities to enhance long-term shareholder value. Strategic Overview Jeffrey B. Kindler, Chairman and Chief Executive Officer of
Pfizer, said: "The combination of Pfizer and Wyeth provides a powerful
opportunity to transform our industry. It will produce the world's premier
biopharmaceutical company whose distinct blend of diversification, flexibility,
and scale positions it for success in a dynamic global health care environment.
The new company will be an industry leader in human, animal and consumer
health. With our combined biopharmaceuticals business, it will lead in primary
and specialty care as well as in small and large molecules. Its geographic
presence in most of the world's developed and developing countries will be
unrivaled." Bernard Poussot, Chairman, President and Chief Executive
Officer of Wyeth, said, "Wyeth's commitment to scientific innovation has
enabled us to build a diversified biopharmaceutical company with leadership in
attractive growth areas such as vaccines, nutritionals and biologics. For
example, Wyeth developed Prevnar, the first pneumococcal vaccine for infants.
In addition, because we were early to see the potential of biotechnology to
create life-changing medicines, we now have a strong franchise which includes
Enbrel, the number one biotechnology product in the world. With our business
focused on prevention and wellness, Wyeth is well positioned in today's rapidly
changing health care environment. Our employees should be enormously proud of
what we have built and confident that combining with Pfizer will accelerate our
pursuit of innovative new medicines to meet critical unmet patient needs. Wyeth
and Pfizer are highly complementary businesses, and together we can build the
best diversified health care company in the world. We believe we can better
execute our strategy and can accomplish far more together in the years ahead
than either company could have achieved on its own." Mr. Kindler continued, "With this combination, Pfizer
will offer patients around the world a uniquely broad and diversified portfolio
of biopharmaceutical innovations through business units--each one focused on
different customer needs and backed by the resources of a premier global organization.
By combining the spirit of small, agile enterprises with our combined scale,
Pfizer will advance its mission of working together toward a healthier
world." Over the last two years, Pfizer has become a leaner, more
disciplined, and far stronger company that is now capable of - and has
demonstrated - superior and consistent execution of its strategies and
commitments. As separately announced today, for example, Pfizer achieved its
2008 objectives despite the challenging economy, including meeting or exceeding
its financial guidance and cost-reduction target. With this essential foundation established, the combination
with Wyeth meaningfully advances in a single transaction each of the strategic
priorities that Pfizer has identified and pursued over the last two years,
including: * Enhancing the in-line and pipeline
patent-protected portfolio in key "Invest to Win" disease areas, such as Alzheimer's disease,
inflammation, oncology, pain and psychosis; * Becoming a top-tier player in biotherapeutics
and vaccines; * Accelerating
growth in emerging markets; * Creating new
opportunities for established products; * Investing in complementary businesses; and * Creating a
lower, more flexible cost base. Mr. Kindler added, "Over the last several years,
Wyeth's leadership and its employees have done an outstanding job creating a
strong, diversified biopharmaceutical company. The people, products, and
technologies that Wyeth brings to the new company will enhance our scientific capabilities
and drive further commercial innovation to improve the health of the patients
we serve. The compelling combination of Pfizer and Wyeth allows us to advance
our newly strengthened organization to the next level by harnessing the talents
of the best people from both companies. This will enable us to accelerate
significantly our progress along 'Our Path Forward' as we pursue our mission of
applying innovative science to improve world health." Global Biopharmaceutical Leadership and Business Diversification The combination of Pfizer and Wyeth will create the world's
premier biopharmaceutical company with a broad range of therapeutic solutions
for many health challenges and preventive care. For Patients Today - A Broad Portfolio of Health Care Solutions
and Treatments The combined company will offer customers and patients a
broad range of products for every stage of life--with top tier portfolios in
key therapeutic areas such as cardiovascular, oncology, women's health, central
nervous system, and infectious disease and a diverse product portfolio that
includes 17 products with more than $1 billion each in annual revenue. Pfizer
will be the second largest specialty care provider, with products including the
world's leading biologic, Enbrel; Prevnar, the world's largest-selling vaccine;
Sutent for cancer; Geodon for schizophrenia; and Zyvox for infection. The
transaction also builds upon Pfizer's position as a global leader in animal
health, with strong product lines in attractive segments, for companion
animals, biologics and anti-infectives. For Patients Tomorrow - A Diverse The new company will have more resources to invest in
research and development than any other biopharmaceutical company and access to
all leading scientific technology platforms, including vaccines, small and
large molecules, nutritionals and consumer products. The combination also brings together a robust pipeline of
biopharmaceutical research and development projects, including programs in
diabetes, inflammation/immunology, oncology and pain, as well as significant
opportunities in Wyeth's Alzheimer's disease pipeline, which has a number of
compounds in development, including phase three biotech compound Bapineuzumab.
These will be added to the exciting agents currently in early and later stage
development at Pfizer for Alzheimer's disease, illustrating the breadth and
depth the new company will be able to use in targeting the diseases that most
affect patients. The new company will have an enhanced ability to innovate,
operating as focused business units tailored to patients and other customers.
Each business unit will oversee product development from clinical trials to
commercialization. This approach will allow for rapid decision-making and a
more efficient use of resources and, as a result, will enhance the company's
ability to invest in long-term opportunities. The combination will also provide
additional high quality and high volume manufacturing capabilities, including
Wyeth's For Patients Everywhere - A Strong Global Presence Geographically, the combination will enhance Pfizer's and
Wyeth's compelling portfolios in important growth areas. Based on IMS data, the
combined company will be number one in terms of biopharmaceutical revenues in
the United States with an approximately 12% market share; in Europe with an
approximately 10% share; in Asia (ex-Japan) with an approximately 7% share; in
Japan with a 6% share; and in Latin America with a 6% share. Pfizer and Wyeth's combined presence will be significant in
high-growth emerging markets, such as Latin America, the Middle East and Conditions The proposed transaction is subject to customary closing
conditions, including approval by the stockholders of Wyeth, notification and
clearance under certain antitrust statutes. In addition, the proposed
transaction is subject to Pfizer's financing sources not declining to provide
the financing due to a material adverse change with respect to Pfizer or Pfizer
failing to maintain credit ratings of A2/A long-term stable/stable and A1/P1
short term affirmed. There are no other financing conditions to closing in the
merger agreement. Pfizer and Wyeth expect the transaction to close at the end
of the third quarter or during the fourth quarter 2009. Advisors Pfizer's lead financial advisors are Bank of America Merrill
Lynch, Goldman Sachs and J.P. Morgan. Barclays and Citigroup are acting as
financial advisors. Its legal advisor is Cadwalader, Wickersham & Taft LLP.
Wyeth's financial advisors are Morgan Stanley and Evercore Partners and its legal
advisor is Simpson Thacher & Bartlett LLP. In addition, Wachtell, Lipton,
Rosen & Katz served as counsel to Wyeth's Board of Directors. ABOUT PFIZER Pfizer Inc, founded in 1849, is dedicated to better health
and greater access to health care for people and their valued animals. Every
day, approximately 81,900 colleagues in more than 150 countries work to
discover, develop, manufacture and deliver quality, safe and effective
prescription medicines to patients. ABOUT WYETH Wyeth is one of the world's largest research-driven
pharmaceutical and health care products companies. It is a leader in the
discovery, development, manufacturing and marketing of pharmaceuticals,
vaccines, biotechnology products, nutritionals and non-prescription medicines
that improve the quality of life for people worldwide. The Company's major
divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort
Dodge Animal Health. Source: Pfizer Press
Release |
* Cytomegalovirus (CMV) infects approximately 86 000
newborns in the * The vaccine is
expected to enter phase II clinical trials in 2009 "We are happy to gain access to a promising vaccine
candidate for the prevention of cytomegalovirus infections, which are
particularly problematic during pregnancy as they can cause permanent
disability in newborns", said Dr. Andrin Oswald, CEO of Novartis Vaccines
and Diagnostics. AlphaVax is responsible for finalization of phase I clinical
trials, and will provide the clinical trial material for the phase II trials.
Novartis will be responsible for the development of the CMV program for phase
II clinical trials onwards as well as for registration and world-wide
commercialization. The AlphaVax vaccine candidate is based on an alphavirus
replicon particle encoding CMV phosphoprotein 65, IE1 (immediate early protein
1) and soluble gB protein. Novartis signed a definitive agreement to acquire rights to
AlphaVax' investigational CMV program for an upfront payment of USD 20 million,
which also grants rights of first negotiation to AlphaVax' preclinical
respiratory syncytial virus (RSV) program. In addition Novartis has an option
to make an equity investment at the end of phase II clinical trials for 4
million shares. Under the terms of the agreement AlphaVax will be eligible for
milestones and royalties. About Novartis Novartis AG provides healthcare solutions that address the
evolving needs of patients and societies. Focused solely on healthcare,
Novartis offers a diversified portfolio to best meet these needs: innovative
medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic
tools and consumer health products. Novartis is the only company with leading
positions in these areas. In 2007, the Group's continuing operations (excluding
divestments in 2007) achieved net sales of USD 38.1 billion and net income of
USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D
activities throughout the Group. Headquartered in |
New Once-Daily Treatment from Market Leader Shows Significant Efficacy over 24 Hours Many People with Incontinence Conditions Suffer without Seeking Medical Help, Recent NIH Report Shows Structurally related to the most prescribed OAB medication, Pfizer’s Detrol® LA (tolterodine tartrate extended release capsules), TOVIAZ can help regulate the involuntary contractions of the bladder associated with OAB. These contractions cause frequent, sudden urges to urinate. The two efficacious and well-tolerated doses of TOVIAZ, 4 mg and 8 mg, allow dosing flexibility to optimize treatment based on the individual patient response and tolerability. “The emotional and social implications for people who suffer from OAB are challenging, yet the condition remains underdiagnosed and highly undertreated,” said Nancy Muller, executive director, National Association For Continence. “We need to encourage people with OAB symptoms to stop simply coping and start talking to their doctors about finding treatment approaches that work for them. New treatments, like TOVIAZ, offer healthcare professionals another option to help their patients.” Symptoms of OAB can have a profound effect on workplace productivity, social and sexual activity and sleep. Overactive bladder may also lead to other health problems, such as falls and fractures, urinary tract infections and skin disorders, sleep problems and depression. Despite the impact of OAB on patients’ lives, research, including a March 2008 National Institutes of Health (NIH) report, concludes that the embarrassment and stigma associated with incontinence can cause sufferers to try to hide the condition from families, friends and even their doctors. As a result, many with incontinence conditions suffer without seeking help. “Pfizer is proud to offer TOVIAZ, a new treatment for OAB symptoms that builds on our strong heritage in urology,” said Jim Maffezzoli, senior director, group leader, Pfizer. “We will continue to partner with physicians and patients to provide extensive support and education to help enhance treatment success.” Dr. Victor Nitti, professor and vice chairman of urology at the TOVIAZ Data Demonstrate Efficacy, Safety In clinical studies, the most commonly reported adverse event was dry mouth (incidence of 7 percent for placebo; 19 percent for TOVIAZ 4 mg; 35 percent for TOVIAZ 8 mg). Most cases of dry mouth were mild to moderate with less than one percent of patients discontinuing TOVIAZ due to dry mouth. There was a low incidence of constipation (2 percent with placebo; 4 percent with 4 mg; 6 percent with 8 mg). TOVIAZ was evaluated for up to three years in open-label studies, with an adverse event profile similar to that seen in previous trials. TOVIAZ will be available in the Important Safety Information for TOVIAZ and Detrol LA If you have certain stomach problems, glaucoma, or trouble getting urine to pass, you shouldn’t take TOVIAZ or The most common side effects (≥4%) of TOVIAZ are dry mouth and constipation. The most common side effects (≥4%) of DETROL LA are dry mouth, headache, constipation, and abdominal pain. TOVIAZ and DETROL LA, like all medicines, have benefits and risks. There may be other options. Ask your doctor if TOVIAZ or DETROL LA is right for you. For more information, visit TOVIAZ.com. or DETROLLA.com. About Overactive Bladder Overactive bladder affects an estimated one in six Americans; yet it is not necessarily a natural part of aging as many people assume. Overactive bladder can impact a wide range of health-related quality of life issues. However, many people with OAB do not seek medical help due to embarrassment or the belief that nothing can be done to alleviate their symptoms. Permalink: http://mediaroom.pfizer.com/news/pfizer/20081031005701/en |
--Approval recognizes importance of treating osteoporosis in men: an estimated one in five aged over 50 will suffer an osteoporosis-related fracture[1]-- --Expanded EU label includes data showing 35% reduction in new fractures in Aclasta-treated patients who recently suffered a low-trauma hip fracture[2]-- --Aclasta also the only osteoporosis treatment to show 28% reduction in all-cause mortality following a low-trauma hip fracture[2]-- Basel, September 30, 2008 - The European Commission has approved once-yearly Aclasta®* (zoledronic acid 5 mg) for the treatment of osteoporosis in men who are at increased risk of fractures, and broadened the Aclasta label to include reduction of new clinical fractures in both men and postmenopausal women with osteoporosis who have recently suffered a hip fracture. Osteoporosis is an important health concern for men, with an estimated one out of five over the age of 50 experiencing an osteoporotic fracture[1]. In cases of hip fracture - one of the most serious consequences of osteoporosis - the mortality rate is higher in men than women in the year following the fracture[3]. Over the first six months, men are approximately twice as likely to die as women of a similar age[3]. "Despite the severity and the large numbers affected, osteoporosis in men has received very little attention," said Steven Boonen, Professor of Medicine at the Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine in In addition, the EU label has been extended to include data from the landmark Recurrent Fracture Trial, involving more than 2,100 patients, showing that once-yearly Aclasta reduced the risk of new clinical fractures by 35% in men and postmenopausal women who have recently had a low-trauma hip fracture (e.g. due to a fall from standing height or less). The new label also includes data from the same study showing that all-cause mortality was significantly reduced by 28% in the Aclasta-treated group compared to those receiving placebo (101 vs. 141 deaths respectively)[2]. Aclasta is the only osteoporosis treatment to demonstrate these benefits in patients after a recent low-trauma hip fracture. "For both men and women, hip fracture can be a potentially life-threatening consequence of osteoporosis," said Prof. Boonen. "Hip fracture is associated with a high risk of morbidity and mortality, and it is encouraging that we now have a treatment proven to reduce the risk of a new fracture after this has occurred." In 2000, approximately 1.6 million hip fractures occurred worldwide[3], and in "At Novartis we are committed to putting the needs of the patient first," said Trevor Mundel, MD, Global Head of Development Functions at Novartis Pharma AG. "More than a quarter of a million patients have already been treated with Aclasta, and these new approvals mean that two new populations can be treated with this once-yearly dosing regimen. This once yearly dosing represents a convenient way to help protect both men and women against the life-threatening consequences of osteoporosis." The EU Commission approval, following a positive opinion issued in July by the Committee for Medicinal Products for Human Use (CHMP), will apply in all 27 EU member states plus Approval was based on pivotal data from the Recurrent Fracture Trial, involving more than 2,100 men and women aged 50 and above who had recently suffered a low-trauma hip fracture[2]. Aclasta was shown to reduce the risk of new clinical fractures by 35% compared to patients receiving placebo[2], and to increase bone mineral density (BMD). The risk of new spine fractures was reduced by 46%[2]. A two-year head-to-head trial comparing Aclasta with weekly oral alendronate provided additional data on the treatment of male osteoporosis[4]. This study involving more than 300 osteoporotic men showed that Aclasta preserved and improved lumbar spine BMD at 24 months[4]. Aclasta, which is administered by once-yearly infusion, was approved in the EU in October 2007 for the treatment of osteoporosis in postmenopausal women. It is now approved in more than 80 countries in this indication and is currently available in more than 70 countries including the Aclasta/Reclast is the only treatment for postmenopausal osteoporosis approved in the EU and US to reduce the risk of fractures at all key sites, including the hip, spine and non-spine (e.g. wrist and rib)[5]. In June 2008, the Food and Drug Administration (FDA) broadened the Reclast is covered by Medicare and most commercial health plans in the Aclasta is also approved in more than 80 countries for the treatment of Paget's disease of the bone, the second most common metabolic bone disorder. Aclasta has a demonstrated tolerability profile. The most common adverse events associated with Aclasta were transient post-dose symptoms such as fever and muscle pain. Most of these symptoms occurred within the first three days following Aclasta administration and resolved within three days. The incidence of such post-dose symptoms can be reduced with the administration of paracetamol or ibuprofen shortly after Aclasta infusion. Zoledronic acid, the active ingredient of Aclasta, is also available under the trade-name Zometa® for use in oncology indications. About Novartis Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in References [1] International Osteoporosis Foundation. Report "Osteoporosis in Men". Available at: www.iofbonehealth.org/download/osteofound/filemanager/publications/pdf/osteoporosis_in_men.pdf. Last access September 2008. [2] Lyles KW, Colon-Emeric CS, Magaziner JS, et al. for the HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007:537:1799-1809. [3] International Osteoporosis Foundation, Facts and statistics about osteoporosis and its impact. Available at: www.iofbonehealth.org/facts-and-statistics.html#factsheet-category-16. Last access September 2008. [4] Novartis, Pharma AG, Data on file. [5] Black DM, Delmas PD, Eastell R, et al. for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007; 356: 1809-1822. [6] Reclast® (zoledronic acid) Injection [Prescribing Information]. Source: Novartis Press Release |
Making Sense of the Cholesterol Drug Vytorin Concerns Q & A with Robert Temple, M.D., FDA’s Director of the Office of Medical Policy at FDA’s Center for Drug Evaluation and Research. Dr. Temple graduated from New York University School of Medicine and completed his residency in internal medicine at Credit: FDA Consumer Health Information e-published on MedicineandBiotech.com August 1st, 2008 Q. What is Vytorin? A. Vytorin is one tablet that combines two cholesterol-lowering drugs—simvastatin (Zocor), a statin made by Merck & Co., and ezetimibe (Zetia), made by Schering-Plough Pharmaceuticals—to help lower bad cholesterol (low-density lipoprotein, or LDL) further. Simvastatin works in the liver to prevent the formation of cholesterol (as do all statin medications), while ezetimibe works by preventing the absorption of cholesterol from the intestine. Q. What is the ENHANCE study? A. About four years ago, Merck and Schering-Plough began a study—Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression, or ENHANCE—that compared the effect of ezetimibe combined with simvastatin (Vytorin) to simvastatin alone. The patients in the study were people with a genetic condition of very high cholesterol called familial hypercholesterolemia. Through images taken with ultrasound, the study evaluated the thickness of the walls of the blood vessels of the neck (carotid arteries). Some studies indicate that increased thickness of the carotid artery walls is associated with an increased risk for cardiovascular disease. ENHANCE did not try to show an effect of Vytorin on important outcomes, such as the chance of a heart attack or stroke. Rather, it was an imaging study of what is often called a biomarker—in this case, the thickness of the blood vessel walls. Q. What were the results of the ENHANCE study? A. While the combination drug Vytorin did better at lowering LDL cholesterol levels than treatment with simvastatin alone, the effect of Vytorin on carotid artery wall thickness was no greater than that observed with simvastatin by itself. The results were disappointing, of course, but they do not give the answer about the value of ezetimibe. At this point we know that ezetimibe lowers cholesterol modestly (not nearly as much as a statin), but we do not have definitive evidence that it lowers the risk for cardiovascular disease. The answer to whether it does should come from a large (18,000-patient) outcome study that will examine the effect of ezetimibe added to simvastatin on cardiovascular outcomes. That study is underway but will not be completed for several years. It is not clear why the lower levels of LDL cholesterol in patients who took Vytorin did not lead to favorable changes in carotid artery wall thickness, compared to patients treated with simvastatin alone. FDA is now reviewing the final results from the ENHANCE study. Q. Does the Vytorin situation call into question the value of lowering cholesterol levels or the benefits of statins? A. No. There is overwhelming evidence from many studies that people with elevated LDL cholesterol—a very well-established risk factor for heart disease—reduce their risk of a heart attack or stroke and death by lowering cholesterol with a statin. FDA's initial approval of cholesterol medications is based on a drug's ability to demonstrate successful lowering of LDL cholesterol. But every statin to date has been shown in a large outcome study to improve cardiovascular outcome, and labeling for all drugs, except for the most recently approved statin, Crestor, states this clearly. A similar finding has been reported for Crestor, but the study has not yet been reviewed by FDA. Q. Why, then, the recent public uncertainty about the value of lowering LDL cholesterol, based on the small Vytorin study? A. We think many people may have misunderstood both the intent and the results of ENHANCE. The study was designed to show an added benefit of ezetimibe on a biomarker and clearly failed to do so. But this does not tell you whether lower cholesterol with ezetimibe will prove useful. The results of the study were released online in the New England Journal of Medicine (NEJM) in January 2008, accompanied by news reports asking whether the results have shaken confidence in the value of lowering cholesterol, even using statins. Although the study could perhaps lead to doubts about ezetimibe—noting again that its lack of effect was on a biomarker—it casts no doubt at all on the value of lowering cholesterol with a statin. Unfortunately, the statins, which have repeatedly been shown to give large reductions in cholesterol levels and a lower risk of dying from heart disease, were also being characterized as having uncertain benefits. In fact, there is no basis at all for questioning the cardiovascular benefits of statins in reducing the rate of death, heart attack, and stroke in people at risk from elevated LDL cholesterol. And we are worried that some people might suddenly stop taking their statins or other preventive medicines, such as antihypertensives, either because they misunderstood news reports or are affected by a more general sense of doubt. We already know that people tend to stop taking all long-term drugs, including statins, when they're on them. And I'm very concerned that aspects of the Vytorin discussion will lead to people becoming indifferent to an extremely important measurement—LDL cholesterol. Q. What are the benefits of lowering your cholesterol? A. Cholesterol is essential to the formation of certain hormones. But where LDL cholesterol levels are too high, they cause or accelerate the development of arteriosclerotic plaques (fatty deposits) in blood vessels in the heart or brain, increasing the chance of a heart attack or stroke. According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death for both women and men in the Q. What is your advice for consumers? A. People should not misunderstand ENHANCE and think it means that elevated LDL cholesterol need not be lowered. To do so could mean significant personal and public health consequences if it drives them away from continuing to reduce their risk of heart disease through lowering their cholesterol. People should not stop taking Vytorin or any other drug containing a statin without their doctor's recommendation, even if they have concerns about the study. Patients can discuss with their doctors whether they should take a larger statin dose or add ezetimibe to control LDL cholesterol adequately. The results with statins make it overwhelmingly clear that controlling LDL cholesterol is essential. This article appears on FDA's Consumer Health Information Web page (www.fda.gov/consumer ), which features the latest updates on FDA-regulated products. Sign up for free e-mail subscriptions at www.fda.gov/consumer/consumerenews.html. For More Information Controlling Cholesterol with Statins www.fda.gov/consumer/updates/statins051608.html FDA Early Communication About an Ongoing Data Review for Ezetimibe/Simvastatin (marketed as Vytorin), Ezetimibe (marketed as Zetia), and Simvastatin (marketed as Zocor) www.fda.gov/cder/drug/early_comm/ezetimibe_simvastatin.htm FDA's Center for Drug Evaluation and Research National Heart, Lung, and www.nhlbi.nih.gov/health/infoctr/ |
--Clinical data showing unprecedented 89% reduction in risk of GIST relapse with use of Glivec after surgery are basis for FDA, EMEA, Swissmedic filings— --Historically, one in two patients experienced recurrence of GIST after surgery— --Regulatory submissions reflect continued commitment to bringing new therapeutic approaches to patients with rare diseases— Basel, August 27 2008 - Novartis announced that Glivec® (imatinib)* has been granted priority review status by the US Food and Drug Administration (FDA) as the first therapy to be reviewed for use after surgery in kit-positive gastrointestinal stromal tumors (GIST). FDA priority review status is granted to therapies that could potentially fill a currently unmet medical need and accelerates the standard review timing from ten to six months[1]. Similar regulatory submissions have been filed in the European Union and The Glivec submissions are based on data from a Phase III, double-blind, randomized, multicenter, international study of more than 700 GIST patients who had surgery to remove their tumors. The results showed a dramatic 89% reduction in risk of GIST returning after surgery (adjuvant setting) in patients treated with Glivec versus placebo[2]. In early 2007, the study met its primary efficacy endpoint, showing an advantage for Glivec in recurrence-free survival. At that time, following the recommendation of the independent study data monitoring committee to stop the trial accrual early, the study investigators made public the interim results and offered Glivec to patients receiving placebo[3]. Approximately half of all patients with newly diagnosed GIST are considered candidates for surgical resection, or removal of their tumors. Of those who have the surgery, about half will suffer a recurrence[4]. If approved for this indication, Glivec will be the first treatment option available to GIST patients after surgery to reduce the risk of disease recurrence or to possibly prevent the disease from returning. "FDA priority review status acknowledges the potential for Glivec to become the first post-surgery treatment available to GIST patients and may soon create a fundamental shift in the treatment of this disease," said Herve Hoppenot, Executive Vice President, Chief Commercial Officer, Novartis Oncology. Glivec is currently indicated in both the Filing data The study on which the regulatory filing is based compared the recurrence-free survival of GIST patients taking Glivec 400 mg/day versus placebo for one year immediately following surgery. The results showed that 98% of patients receiving Glivec remained recurrence free at one year following surgery compared to approximately 82% of those receiving placebo[3]. This shows that as a result of adjuvant therapy with Glivec, there was an 89% reduction in risk of GIST returning[2]. The study, known as ACOSOG Z90001, was conducted at multiple cancer centers throughout the The investigators reported that Glivec therapy was well tolerated by most patients, with side effects similar to those observed in previous clinical trials with Glivec. These include nausea, diarrhea and swelling (edema)[3]. About Gastrointestinal Stromal Tumors (GIST) Gastrointestinal stromal tumors (GIST) belong to a group of cancers known as soft tissue sarcomas. They are the most common sarcomas and can be found most often in the stomach and small intestine. The incidence of GIST is estimated to be 4,500 - 6,000 new cases per year in the About Glivec Glivec is approved in more than 90 countries, including the US, EU and Japan, for the treatment of all phases of Ph+ CML. Glivec is also approved in the EU, US and other countries for the treatment of patients with Kit (CD117)-positive gastrointestinal tumors (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (metastasized). In The effectiveness of Glivec is based on overall hematologic and cytogenetic response rates and progression-free survival in CML, on hematological and cytogenetic response rates in Ph+ ALL, and on objective response rates in GIST and DFSP. There are no controlled trials demonstrating increased survival. Not all indications are available in every country. Glivec contraindications, warnings and adverse events The majority of patients treated with Glivec in clinical trials experienced adverse events at some time. Most events were of mild to moderate grade and treatment discontinuation was not necessary in the majority of cases. The safety profile of Glivec was similar in all indications. The most common side effects included nausea, superficial edema, muscle cramps, skin rash, vomiting, diarrhea, abdominal pain, myalgia, arthralgia, hemorrhage, fatigue, headache, joint pain, cough, dizziness, dyspepsia and dyspnea, dermatitis, eczema, fluid retention, as well as neutropenia, thrombocytopenia and anemia. Glivec was generally well-tolerated in all of the studies that were performed, either as monotherapy or in combination with chemotherapy, with the exception of a transient liver toxicity in the form of transaminase elevation and hyperbilirubinemia observed when Glivec was combined with high dose chemotherapy. Rare/serious adverse reactions include: sepsis, pneumonia, depression, convulsions, cardiac failure, thrombosis/embolism, ileus, pancreatitis, hepatic failure, exfoliative dermatitis, angioedema, Stevens-Johnson syndrome, renal failure, fluid retention, edema (including brain, eye, pericardium, abdomen and lung), hemorrhage (including brain, eye, kidney and gastrointestinal tract), diverticulitis, gastrointestinal perforation, tumor hemorrhage/ necrosis, hip osteonecrosis/avascular necrosis. Patients with cardiac disease or risk factors for cardiac failure should be monitored carefully and any patient with signs or symptoms consistent with cardiac failure should be evaluated and treated. Cardiac screening should be considered in patients with HES/CEL, and patients with MDS/MPD with high level of eosinophils (echocardiogram, serum troponin level). Glivec is contraindicated in patients with known hypersensitivity to imatinib or any of its excipients. Women of childbearing potential should be advised to avoid becoming pregnant while taking Glivec. About Novartis Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on growth areas in healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in References [1.] Fast Track, Priority Review and Accelerated Approval. [2.] Internal data. [3.] Z9001: A Phase III Randomized Double-blind Study of Adjuvant STI571 (Gleevec®) Versus Placebo in Patients Following the Resection of Primary Gastrointestinal Stromal Tumor (GIST). http://www.cancer.gov/clinicaltrials/ACOSOG-Z9001. Accessed June 2008. [4.] Van den Abbeele A., Benjamin R., Blanke C, et al. Clinical Management of GIST. Recurrence patterns and prognostic factors for survival. 2003;1-24. [5.] American Cancer Society. Cancer Reference Information. Detailed Guide for Gastrointestinal Stromal Tumors. Key Statistics. http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1x_What_Are_the_Key_Statistics_About_Gastrointestinal_Stromal_Tumors.asp?rnav=cri. Accessed 22 February 2008. [6.] * Known as Gleevec® (imatinib mesylate) tablets in the Source: Novartis Press Release |
- Pentacel® vaccine is the first 5-in-1 pediatric combination for immunization against diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (Hib) - 6 weeks through 4 years of age (prior to fifth birthday). Pentacel® vaccine is the first and only four-dose diphtheria, tetanus, and acellular pertussis (DTaP)- based combination vaccine for use in infants and young children in the Pentacel® vaccine is approved for administration as a four-dose series at 2, 4, 6 and 15-18 months of age. The first dose may be given as early as 6 weeks of age. According to the current Recommended Childhood Immunization Schedule of the U.S. Centers for Disease Control and Prevention (CDC), up to 23 injections are needed by the time a child reaches 18 months of age with single-entity vaccines. The use of Pentacel® vaccine could reduce that number of shots by seven. “Pentacel® vaccine will help simplify the immunization schedule by reducing the number of injections infants and young children will receive in their first two years of life,” said Wayne Pisano, President and Chief Executive Officer, sanofi pasteur. Pentacel® vaccine has been used in and parents in the “The FDA approval of Pentacel® vaccine is great news for parents and pediatricians who want to reduce the stress of well-baby visits,” said Tina Q. Tan, M.D., infectious disease specialist, Children’s Pentacel® vaccine is also the first five-component (pentavalent) pediatric combination vaccine in the U.S. to contain sanofi pasteur’s five acellular pertussis antigens, which are also used in its DTaP vaccine for children (DAPTACEL®a vaccine, licensed in 2002) and its tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for adults and adolescents (Adacel®b vaccine, licensed in 2005). Pertussis is commonly known as whooping cough because of the sound some patients—especially children—make while gasping for air during coughing spells. The FDA licensure of Pentacel® vaccine is based on the results of multi-center clinical studies conducted in the and to other single-entity vaccine formulations (study 494-01). In clinical studies, local and systemic reactions following administration of Pentacel® vaccine were reported at rates consistent with those of the separately administered vaccines used in each trial. The most common local and systemic adverse reactions to Pentacel® vaccine include injection site redness, swelling and tenderness; fever, fussiness and crying. Other adverse reactions may occur. Known systemic hypersensitivity reaction to any component of Pentacel® vaccine or a life-threatening reaction after previous administration of the vaccine or a vaccine containing the same substances are contraindications to vaccination. The decision to give Pentacel® vaccine should be based on the potential benefits and risks; if Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid; or if adverse events have occurred in temporal relation to receipt of pertussis-containing vaccine. Encephalopathy within 7 days of administration of a previous dose of a pertussis-containing vaccine or a progressive neurologic disorder is a contraindication. Vaccination with Pentacel® vaccine may not protect all individuals. Before administering Pentacel® vaccine, please see accompanying full Prescribing Information. The full Prescribing Information for Pentacel® vaccine is available on www.pentacel.com and www.vaccineshoppe.com . More than 14 million doses of Pentacel® vaccine have been distributed in summer. Sanofi Pasteur’s In 2005, sanofi pasteur continued its tradition of innovation by introducing MenactraÒf vaccine to protect against meningococcal disease, and Adacel vaccine as a booster dose for protection against tetanus, diphtheria and pertussis in both adults and adolescents 11-64 years of age. About Sanofi-aventis Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi Pasteur, the vaccines division of sanofi-aventis Group, provided more than 1.6 billion doses of vaccine in 2007, making it possible to immunize more than 500 million people across the globe. A world leader in the vaccine industry, sanofi pasteur offers the broadest range of vaccines protecting against 20 infectious diseases. The company's heritage, to create vaccines that protect life, dates back more than a century. Sanofi Pasteur is the largest company entirely dedicated to vaccines. Every day, the company invests more than EUR1 million in research and development. For more information, please visit: www.sanofipasteur.com or www.sanofipasteur.us . Source: Sanofi-aventis Press Release |
--Extavia is Novartis brand for interferon beta-1b - an established therapy with more than 700,000 patient-years' experience to date[1]-- --Launch of Extavia for early and relapsing forms of multiple sclerosis (MS) planned for US and --Novartis committed to MS through extensive research and development programs, including novel oral therapy FTY720 currently in Phase III-- --MS, a devastating disease causing progressive disability, affects an estimated 2.5 million people worldwide, including many young adults[2]-- Extavia is the Novartis branded version of interferon beta-1b, a first-line disease-modifying therapy injected every other day for the treatment of MS. Interferon beta-1b has been available globally for more than 13 years and is supported by more than 700,000 patient-years of experience[1].
Formerly known as NVF233, Extavia is the same medicine as Betaferon®/Betaseron®, which is marketed by Bayer-Schering and was the first beta interferon treatment for MS. Novartis gained rights to its own branded version of this medicine in agreements with Bayer-Schering related to the acquisition of Chiron. "Novartis is committed to MS and to providing effective treatments for patients with this disease," said Trevor Mundel, MD, Head of Global Development Functions at Novartis Pharma AG. "The approval of Extavia means we are able to offer the MS community a current standard of care while preparing for the introduction of innovative therapies such as FTY720." Novartis also recently filed for approval of interferon beta-1b with the US Food and Drug Administration. Launches in the US and EU are planned for the first half of 2009, in line with an agreement with Bayer-Schering that established the opportunity for Novartis to introduce its own branded version of interferon beta-1b. By the end of 2009, Novartis also plans to file for approval of the innovative oral therapy FTY720 (fingolimod). Results of an ongoing Phase II study extension presented in April show sustained benefits in patients with relapsing MS after three years of treatment with FTY720. Data showed that 68-73% of patients in the study remained free from relapses after three years' continuous treatment[3].
A number of other compounds for treating MS are also in early stage development by Novartis.
Multiple sclerosis is the most common disorder of the central nervous system in young adults. It is a progressive and debilitating disorder caused by the destruction of myelin, which helps neurons carry electrical signals in the brain. MS causes problems with muscle control and strength, vision, balance, sensation and cognitive function2. MS typically presents in relapsing forms involving acute self-limiting attacks of neurological dysfunction (or "relapses") followed by complete or partial restoration of functions[4].
In the EU, Extavia is approved for patients with relapsing-remitting MS, the most common form of the disease involving relapses followed by complete or partial restoration of function, and for a steadily worsening form of the disease known as secondary progressive MS with relapses. In addition, Extavia is approved to treat patients with early MS who: --Have experienced a single episode involving loss of myelin (or "demyelinating event") --Have an active inflammatory process that is severe enough to need treatment with intravenous corticosteroids, if alternative diagnoses have been excluded r--Are at high risk of developing clinically definite MS. About Novartis Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on growth areas in healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in References [1] Data on file. [2] Multiple Sclerosis International Federation at www.msif.org Accessed 15 May 2008. [3] Comi G et al. Oral FTY720 (fingolimod) in patients with relapsing multiple sclerosis. 3-year extension shows sustained low relapse rate and MRI activity. Abstract presented at 60th annual meeting of [4] National Multiple Sclerosis Society at www.nationalmssociety.org, Accessed 15 May 2008.
Source: Novartis Press Release |
Raritan, NJ (March 28, 2008) – Ortho-Clinical Diagnostics announced U.S. Food and Drug Administration approval of a new diagnostic assay for the detection of antibodies to Human Immunodeficiency Virus types 1 and/or 2 (anti HIV-1 and anti HIV-2). The new VITROS® Anti-HIV 1+2 assay1 can be run in a fully automated, random access format on the VITROS ECi/ECiQ Immunodiagnostic System, with results readily available in less than 50 minutes. This FDA approval and availability to laboratories in the The VITROS Anti-HIV 1+2 assay can help meet the demand on laboratories created by new U.S. Centers for Disease Control and Prevention (CDC) testing recommendations. The CDC now recommends routine, voluntary HIV testing in all health care settings, including health clinics and emergency rooms, for all individuals ages 13 to 64 without written informed consent. In addition, testing is recommended at least once a year for those at high risk.2 By latest estimates, approximately 1,039,000 to 1,185,000 people in the Two multicenter research teams supported in part by the National Institute on Drug Abuse, National Institutes of Health, have independently determined through the development of computer models that routine screening for HIV in health care settings is as cost effective as screening for other conditions such as breast cancer and high blood pressure, and can provide important health and survival benefits. The studies also suggest that screening that leads to a diagnosis of HIV infection may further lower health care costs by preventing high-risk practices and decreasing virus transmission.4 The VITROS Anti-HIV 1+2 Assay has been co-developed with Chiron, a business of Novartis Vaccines and Diagnostics Inc. About the VITROS ECi/ECiQ Immunodiagnostic System The expanding VITROS ECi/ECiQ Immunodiagnostic System test menu now includes more than 45 tests worldwide for the sensitive measurement of thyroid function, reproductive health and fertility, bone metabolism, anemia, metabolic, oncology, emergency cardiology, and infectious diseases. About Ortho-Clinical Diagnostics Ortho-Clinical Diagnostics, a Johnson & Johnson company, is a leading provider of high-value diagnostic solutions for the global health care community. Committed to developing the most advanced tests for early detection or diagnosis of disease, the company brings products to market that provide timely information and help to facilitate medical decisions. Ortho-Clinical Diagnostics also provides blood screening and typing products that help to ensure the safety of the world’s blood supply. In addition, through its VITROS MicroSlide and enhanced chemiluminescence technologies, the company has transformed the way that clinical laboratories perform testing. Worldwide, health care professionals rely on Ortho-Clinical Diagnostics for innovative diagnostic solutions and services that promote effective diagnoses and enhance patient care. For more information, visit www.orthoclinical.com. 1 Refer to the VITROS Immunodiagnostic Products Anti-HIV 1+2 Reagent Pack and VITROS Products Anti-HIV 1+2 Calibrators Instructions for Use for Warnings and Limitations 2 CDC. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 2006; 55 (No. RR-14):1-17. 3 Glynn M, Rhodes P. Estimated HIV prevalence in the 4 http://www.drugabuse.gov/newsroom/05/NR2-09.html Source: J&J Press Release Share your Favorite Biotech/Pharma/Medicine/Clinical Trials articles on Your Helix!-Professional Networking Site Designed for Biotech/Pharma Community: |
Sanofi-aventis’ SoloSTAR® Disposable Insulin Injection Pen for Diabetes Patients Receives the Prestigious GOOD DESIGN Award February 2008. The Chicago Athenaeum Museum of Architecture and Design has awarded a 2007 GOOD DESIGN™ Award for the new SoloSTAR® disposable insulin injection pen for people with type 1 and type 2 diabetes. “LANTUS® SoloSTAR® and APIDRA® SoloSTAR®, the results of over four years of intensive development, have been designed in dialogue with patients, nurses and doctors and meet the high standards of the industry,” said Paul Jansen, Global Head Medical Devices, Sanofi-aventis. “SoloSTAR® represents a design for social good and for humanitarian concerns”. When choosing a specific insulin pen for an individual patient, clinicians consider the patient's insulin regimen, lifestyle, and other factors that may affect the ability to use a particular device, such as manual dexterity and visual acuity. Therefore certain characteristics of a given insulin pen may make it preferable for patients. The outstanding design of SoloSTAR® using breakthrough technology contributes to making this patients’ and clinicians’ choice easier. SoloSTAR® provides a delivery option that may be more acceptable and more convenient to use in comparison with other delivery systems, thus may promote patient compliance, which could help achieve and maintain glycemic control. A recent survey of LANTUS® SoloSTAR® use in everyday clinical practice, involving more than 2000 people with diabetes (16% with manual dexterity problems and 15% with poor eyesight not corrected by glasses) showed that more than 95% of participants declared to be “satisfied” or “very satisfied” with using SoloSTAR® to inject insulin, irrespective of diabetes type or previous device experience. Healthcare professionals involved in teaching the people in this survey how to use LANTUS® SoloSTAR® found SoloSTAR® to be easy learn and easy to use for people with diabetes. SoloSTAR® also operates with a lower injection force and a recent study found that SoloSTAR® required 31% less injection force than the Novo Nordisk FlexPen® and 54% less force than the Eli Lilly Humulin/Humalog pen. “Insulin injection with SoloSTAR® brings flexibility, satisfaction for the patients, and an opportunity for earlier initiation of insulin therapy which may contribute to better long term glycaemic control”, Denis Raccah, Professor of Endocrinology, University Hospital Sainte Marguerite, France, added. About SoloSTAR® SoloSTAR® is a new, easy-to-use disposable pen for administration of LANTUS® and APIDRA®. SoloSTAR®, allows to administer doses from 1 up to 80 units, in one unit increments, in one injection. SoloSTAR offers a 25% greater maximum capacity than other insulin pens. Consequently, the administration until 80 units of insulin can be done with only one injection. SoloSTAR uses a simple, intuitive design with easy-to-read display featured and requires only a few steps to use it properly. SoloSTAR® is small, discreet and eliminates the need for the patient to change insulin cartridges. Easy-to-use and easy-to-inject, SoloSTAR® reduces the injection force by 30% or more in comparison to other most broadly available pens in its class. Lantus® SoloSTAR® and APIDRA® SoloSTAR® were approved by the EMEA in September 2006; LANTUS® SoloSTAR® was approved by the FDA in April 2007. LANTUS® SoloSTAR® and APIDRA® SoloSTAR® are launched in The elegant exterior design of Lantus® and Apidra® SoloSTAR® and its ease of use due to advanced technology is the result of the collaboration with DCA Design International Ltd. in Great Britain DCA Company. About Sanofi-aventis’ pen portfolio Sanofi-aventis having 85 years of innovation in the diabetes is committed to offering people with diabetes an integrated system of insulin products and delivery devices. In addition to the SoloSTAR®, the pen portfolio available for LANTUS® and APIDRA® includes the OptiSet® disposable pen, the OptiClik® and OptiPen® Pro reusable pens, and the Autopen® 24 from Owen Mumford. About LANTUS® (insulin glargine [rDNA origin]) LANTUS® is indicated for once-daily subcutaneous administration in the treatment of adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia and for adult and pediatric patients (6 years of age and older) with type 1 diabetes mellitus. LANTUS® demonstrates a consistent slow, prolonged absorption and a relatively constant concentration/time profile over 24 hours. About APIDRA® (insulin glulisine [rDNA origin]) APIDRA® is a rapid-acting insulin analog with a unique zinc-free molecular structure that maintains a rapid onset and a short duration of action, indicated for adult patients with type 1 and type 2 diabetes. APIDRA® offers patients mealtime dosing flexibility—it can be taken 15 minutes before or within 20 minutes after starting a meal. APIDRA® is also flexible for use in patients with a variety of body types, from lean to obese. About Diabetes Diabetes is a chronic, evaluative widespread disease in which the body reduces or does not produce or properly use insulin – the hormone needed to convert glucose (sugar) into energy. More than 240 million people worldwide are living with the disease. It is estimated that near 250 million people worldwide have diabetes, the number is expected to reach some 380 million within 20 years. It is estimated more than 20 million Americans have diabetes, including an estimated 6.2 million who remain undiagnosed. At the same time, approximately half of those diagnosed are not achieving the general blood sugar control standard of A1C <7% recommended by the American Diabetes Association and the European Association for the Study of Diabetes (ADA/EASD). The A1C test reflects average blood glucose levels over a two- to three-month period. Without proper insulin production and action, glucose remains in the blood, leading to chronic hyperglycaemia (raised blood sugar). This can result in short and long-term complications, many of which, if not prevented and left untreated, can be fatal. All have the potential to reduce the quality of life of people with diabetes and their families. The most common long-term complications are: - Diabetic nephropathy (kidney disease), which may result in total kidney failure and in the need for dialysis or kidney transplant. - Diabetic eye disease (retinopathy and macular oedema), damage to the retina of the eye which can lead to vision loss. - Diabetic neuropathy (nerve disease), which can ultimately lead to ulceration and amputation of the feet and lower limbs. - Cardiovascular disease, which affects the heart and blood vessels and may cause fatal - complications such as coronary heart disease (leading to a heart attack) and stroke. Diabetes is the fourth leading cause of death by disease globally. Every year, 3.8 million people die from diabetes-related causes. About GOOD DESIGN The Museum’s historic GOOD DESIGN program was founded in About Sanofi-aventis Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. References: For easy to inject Owens DR. Comparison of insulin pen devices reveals lower injection force of Solostar® compared with novo Flexpen® and lilly® disposable pen; Diabetes Technology Meeting 25–17 October 2007, San Francisco, CA, USA. Journal of Diabetes Science and Technology, March 2008; Abstract OWEN70184; In press. Clarke A, Spollett G. Dose accuracy and injection force dynamics of a novel disposable insulin pen. Expert Opin. Drug Deliv. (2007) 4(2):165-174. For easy to use and patient’s satisfaction Carter J et al. Usability, participant acceptance and safety of SoloStar in an observational survey in everyday clinical practice; Diabetes Technology Meeting 25–17 October 2007, Source: Sanofi-Aventis Press Release |
Affymetrix Launches World's Most Comprehensive Solution for Clinical Drug Metabolism Studies for Pharmaceutical Research --Drug Metabolizing Enzymes and Transporters (DMET) Early Access Solution Enables Pharmaceutical Researchers to Assess all Clinically Relevant ADME Markers in a Single Assay-- SANTA CLARA, Calif-Jan. 24, 2008--Affymetrix Inc. announced the availability of its Drug Metabolizing Enzymes and Transporters (DMET) Early Access solution, currently the world's most comprehensive method for assaying the genetics of drug metabolism. The DMET offering profiles more than 1,069 drug metabolism biomarkers, including 172 "core" genetic markers. Data is automatically interpreted into a common format that can be integrated into clinical trial workflows. The information enables researchers to make more informed drug-development decisions, which in turn significantly streamlines the drug-development process and, therefore, time to market. The DMET solution is available as a service through Affymetrix' South San Francisco Services Laboratory and Cogenics, a subsidiary of Clinical Data. Both providers have been accepting samples since the fourth quarter of 2007, following the successful completion of a six-week training and certification program to ensure that data is complete, accurate and reproducible. Cogenics is offering DMET as a Good Laboratory Practice (GLP)-compliant service from its Pharmaceutical customers are using the DMET solution to better understand pharmacokinetics, the study of the bodily absorption, distribution, metabolism and excretion (ADME) of drugs. DMET is the only product available with comprehensive coverage of all ADME drug metabolism biomarkers, including common and rare variations, insertions, deletions, copy number, triallelic SNPs and pseudogenes. For the first time, scientists are able to assess all clinically relevant ADME markers in a single assay, unlike previously used single-plex approaches. "Being able to measure a variety of 'core' genetic markers is critical to delivering accurate clinical assays, something the Affymetrix technology is allowing us to achieve. Accurate clinical assays have the ability to deliver improved patient outcomes because the medicines we develop become more directly targeted to the patient's specific needs," said Richard Deane Hockett, senior clinical research physician, group leader for genomic medicine, Department of Diagnostic and Experimental Medicine at Eli Lilly & Co. "We are implementing this technology across the research portfolio in all phases of clinical trials at Lilly." Regulatory authorities have indicated a renewed interest in surveying drug metabolism biomarkers to ensure safer dosing, which in turn reduces the possibility of adverse events and improves patient safety. Just three months ago, the U.S. Food and Drug Administration (FDA) made history by updating the label on the anticoagulant drug, Warfarin, to include information on CYP2C9 and VKCORC1. According to a commentary in Clinical Pharmacology and Therapeutics co-authored by the FDA(1), "Pharmacogenomic data can facilitate our understanding of the sources of variability in drug response and can potentially lead to improved safety and efficacy of drug therapy for individual patients. Through various initiatives, the FDA is encouraging drug developers to apply the rapidly evolving pharmacogenomic tools and integrate these data into the evaluation of patient variability." Michael Caldwell, M.D., Ph.D., director of the Wound Healing Program at Marshfield Clinic, has been using the DMET solution to research the genetics behind an individual's drug response to Warfarin, a drug that if prescribed at the wrong dose can have serious adverse events. "The DMET panel has allowed us to better delineate the stable therapeutic dose of Warfarin for our patients at the initiation of therapy, where risk of complications from the drug are at their highest," said Dr. Caldwell. "Thus our hope is that these studies will enable us to reduce the overall complications of Warfarin therapy by a better prediction of stable therapeutic dose." The DMET solution features easy-to-use patient consent tracking and data translation software to identify functional variants across the panel and to convert genotyping results into standardized star nomenclature, a convention commonly used in the genetic analyses of clinical trials. The automated analysis takes only a few minutes to complete and provides pharmaceutical researchers performing clinical trials with familiar data that can be easily integrated into existing workflows. Previously, this analysis was a manual and time-consuming task as scientists were required to scour literature for relevant answers. "DMET Early Access is the result of an ongoing Affymetrix commitment to develop assays that are targeted at clinical drug development," said Maneesh Jain, senior director of marketing at Affymetrix. "We've been fortunate to work with leading pharmaceutical partners and key medical centers to design and develop an assay that's comprehensive for ADME biomarkers and directly provides information with clinical utility." About Affymetrix Affymetrix GeneChip(R) microarray technology is the industry-standard tool for analyzing complex genetic information. After inventing microarray technology in the late 1980s, Affymetrix scientists have been dedicated to developing innovative products that provide researchers with a more complete view of the genome. These products continue to accelerate genetic research and enable scientists to develop diagnostics and tailor treatments for individual patients by identifying and measuring the genetic information associated with complex diseases. Today, Affymetrix technology is used by the world's top pharmaceutical, diagnostic and biotechnology companies, as well as leading academic, government and not-for-profit research institutes. More than 1,600 systems have been shipped around the world and more than 10,500 peer-reviewed papers have been published using the technology. Affymetrix is headquartered in |
Merck’s Strategic Plan, Pipeline in Progress and Implementation of a New Model -Merck's Pipeline Continues to Progress with Seven Products in Phase III Development- -Company Expects to File Applications for Expanded Indications on GARDASIL and ISENTRESS in 2008- -Merck Intends to Initiate a Sequenced Phase III Program for Anacetrapib in 2008- -Successful Early Launches of GARDASIL, JANUVIA, JANUMET and ISENTRESS- -Reflect Better Alignment of Product Development and Commercialization Efforts; Replicable Model to Reduce Time to Market of New Medicines and Vaccines- -Company Remains on Track to Deliver Long-Term, Double-Digit Compound Annual EPS Growth from 2005 to 2010, Excluding Certain Items- Dec. 11, 2007 - Merck & Co., Inc. hosted its Annual Business Briefing and reviewed the progress the Company has achieved under a strategic plan designed to re-engineer the way Merck develops and distributes medicines and vaccines worldwide. Since 2005, Merck's senior management team has been developing and implementing a new operating model under which customer focus drives drug discovery, development and marketing at the Company, Merck Chairman, President and Chief Executive Officer Richard T. Clark told investors and analysts today at the Merck Annual Business Briefing. "We are realizing the benefits of the successful execution of our strategy. We have created a model for success that encompasses every aspect of our business, including R&D, manufacturing and commercialization," Mr. Clark said. "As a result, Merck has a sustainable business model that will allow us to realize the goals we set for 2010 and to position the Company for future success." During his presentation, Mr. Clark highlighted some of the goals the Company has met or expects to meet by 2010, including: * Launched seven new drugs and vaccines in the past two years, many of them first- or best-in-class * Compound annual revenue growth of 4 percent to 6 percent from 2005 to 2010, including 50 percent of all joint-venture revenue * Double-digit compound annual earnings per share (EPS) growth from 2005 to 2010, excluding certain items * Plan to return product gross margin to pre-ZOCOR levels in 2008 * Reduced clinical development cycle times relative to the pharmaceutical sector "The changes we have made and are continuing to make at Merck are designed to be sustained over the long term. They represent a true model for success," Mr. Clark said. "We have not focused only on short-term successes, but we are making the necessary investments to ensure the success of this Company beyond the year 2010." Merck's Late-Stage Pipeline Continues to Grow Building on the seven U.S. Food and Drug Administration (FDA) approvals Merck has received in the past two years, the Company anticipates regulatory action will be taken in 2008 on two New Drug Applications (NDA) for EMEND for Injection and CORDAPTIVE, the proposed brand name for MK-0524A. Also in 2008, the Company anticipates making two additional NDA filings with the FDA for MK-0524B, simvastatin combined with laropiprant and extended-release niacin, and MK-0364, taranabant, an investigational medication for the treatment of obesity, said Peter S. Kim, Ph.D., president of Merck Research Laboratories. Additionally, Dr. Kim said, the Company anticipates making two supplemental filings with the FDA in 2008: one for GARDASIL, Merck's vaccine for the prevention of cervical cancer, for an expanded indication for adult women through age 45, and one for ISENTRESS, a first-in-class integrase inhibitor for the treatment of HIV-1 infection, for an expanded indication for use in treatment-naïve patients. During his presentation, Dr. Kim also detailed the following seven drug candidates currently in Phase III development: -MK-0524B is a drug candidate that combines the novel approach to raising HDL-cholesterol (HDL-C) and lowering triglycerides from extended-release niacin combined with laropiprant with the proven benefits of simvastatin in one combination product. The candidate already is in Phase III development, and Merck continues to anticipate filing an NDA for MK-0524B in 2008. -MK-0364, taranabant, is a highly selective cannabinoid-1 receptor inverse agonist that in early clinical studies has demonstrated weight loss versus placebo. The Company previously announced the initiation of a targeted Phase III program in 2006. Merck anticipates filing an NDA in 2008. -MK-0974, an investigational oral calcitonin gene-related peptide receptor antagonist, utilizes a new mechanism for the treatment of migraines that has demonstrated efficacy at least comparable to triptans in early clinical studies. The drug candidate entered Phase III development during 2007. The Company anticipates filing an NDA in 2009. -MK-7418, rolofylline, is a Phase III investigational drug being evaluated for the treatment of acute heart failure. Merck acquired the drug candidate as part of the 2007 acquisition of NovaCardia, Inc. and anticipates filing an NDA with the FDA in 2009. -MK-8669, deforolimus, is a novel mTOR (mammalian target of rapamycin) inhibitor being evaluated for the treatment of cancer. The drug candidate is being jointly developed and commercialized with ARIAD Pharmaceuticals, Inc. under an agreement reached in mid-2007. The Company anticipates filing an NDA in 2010. -HEPLISAV, a novel investigational hepatitis B vaccine, currently is being evaluated in a Phase III clinical trial in adults and in patients undergoing dialysis treatment. Merck is jointly developing HEPLISAV with Dynavax Technologies Corporation under an agreement reached in late 2007. Merck anticipates filing an NDA in 2010 for adults. -MK-0822, odanacatib, is a highly selective inhibitor of cathepsin K enzyme, which is being evaluated for the treatment of osteoporosis. The Phase III program began in mid-2007. Merck anticipates filing an NDA with the FDA in 2012. Dr. Kim also provided an update on the development of MK-0859, anacetrapib, an inhibitor of the cholesterol ester transfer protein (CETP) that in early clinical trials has shown promise in lipid management by raising HDL-C and reducing LDL-cholesterol (LDL-C) without raising blood pressure. "In clinical studies, inhibition of CETP raises plasma HDL-C levels and decreases LDL-C levels, which represents a potential therapeutic intervention to reduce the risk of coronary artery disease," Dr. Kim said. "The safety and tolerability profile of anacetrapib was comparable to placebo in clinical studies conducted to date. In 2008, we plan to initiate a sequenced Phase III program to obtain additional clinical experience in patients before initiating an outcomes study." As of Dec. 11, 2007, Merck's updated pipeline chart includes 25 distinct candidates in Phase I and 15 in Phase II. In addition, there are seven candidates currently in Phase III, one submission currently under FDA review, and another that has received an approvable letter and is awaiting further regulatory action. In its pipeline review, Merck does not include backup candidates; additional indications for candidates in the same therapeutic area; or additional claims, line extensions or formulations for existing products. New Commercial Model More Effective and Efficient Kenneth C. Frazier, executive vice president and president, Global Human Health, provided an update on the early successes of Merck's ongoing endeavor to align the Company's product research, development and marketing efforts. In his presentation, Mr. Frazier said that the successful launches and strong global uptake of GARDASIL, JANUVIA and JANUMET are the result of a replicable model that continues to evolve. He said that the Merck model is not only proving more cost efficient but is allowing Merck to reduce the time it takes to get new medicines and vaccines into markets around the world. As part of this effort, Merck Global Human Health, aligned with Merck Research Laboratories and Merck Manufacturing, is utilizing the latest technologies and broadening its engagement with customers, physicians and scientific leaders to get needed medicines and vaccines through the development pipeline and to patients sooner, Mr. Frazier said. The strong sales of Merck's new products, coupled with continued strong growth from in-line products, especially SINGULAIR, should allow Merck to offset the impact of the loss of Merck Reaffirms 2007 and 2008 Financial Guidance During his presentation, Executive Vice President and Chief Financial Officer Peter N. Kellogg reaffirmed Merck's previously disclosed financial outlook for 2007 and 2008. "With our 2007 and 2008 guidance, it is clear that our products are driving a healthy top line despite lapping the ZOCOR expiry and the upcoming FOSAMAX exposure," Mr. Kellogg said. "We are very pleased with our results in 2007, and we anticipate continued strong financial performance from our key franchises in 2008. "As I previously noted on Dec. 4, our financial guidance in 2008 represents the next step in our journey to reach our stated 2010 top- and bottom-line goals. Despite the loss of marketing exclusivity for FOSAMAX in the He continued, "As we disclosed in 2005, Merck's new and in-line pharmaceutical products and vaccines are expected to drive revenue at a compound annual growth rate of 4 percent to 6 percent from 2005 through 2010, including 50 percent of the revenues from the joint ventures from which Merck derives equity income. We also expect that we can fully support our expanding pipeline with mid-single-digit compound annual growth in research funding over the same period. The productivity generated by our ongoing cost management initiatives allows Merck to fully capitalize on the promise of our expanding product portfolio while maintaining marketing and administrative expense at 2006 levels." About Merck Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com. Forward-Looking Statement This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements set forth in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference. |
FDA's New Generic Drug Program-GIVE Q&A with Gary J. Buehler, RPh., Director of FDA’s Office of Generic Drugs (OGD) Credit: FDA Consumer Health Information e-published on MedicineandBiotech.com December 1st, 2007 Gary J. Buehler, RPh., is Director of the Office of Generic Drugs (OGD) in FDA's Center for Drug Evaluation and Research (CDER). A graduate of Q: What are generic drugs? A: A generic drug is identical to a brand-name drug in dosage form, safety, strength, route of administration, quality, performance, and intended use. Although the active ingredient is chemically the same as the branded counterpart, a generic drug is typically sold at a substantial discount from the branded product price. Q: If they are the same, why do generic drugs cost less than their brand-name counterparts? A: Creating a drug and conducting clinical trials is expensive. Generic drug makers don't develop a drug from scratch or have to conduct studies to prove safety and effectiveness. As the result, their expenses for bringing generic drugs to market are less. But generic drug makers must show that their product performs in the same way as the brand-name drug. Q: What is FDA's role regarding generic drugs? A: CDER ensures that both brand-name and generic drugs are safe and effective, and that their health benefits outweigh their known risks. And, just as it does with brand-name drugs, the agency closely inspects generic makers' production sites and assures products approved are manufactured according to regulations regarding good manufacturing practices. Health professionals and consumers can be assured that FDA-approved generic drugs have met the same rigid manufacturing standards as the brand-name drug. Q: What is the Generic Initiative for Value and Efficiency (GIVE) program? A: GIVE is an initiative aimed at optimizing OGD's generic drug review process to increase efficiency. The goals of GIVE are to approve higher numbers of applications for generic products and expedite review of applications for which there are few generics available. Q: What will the benefits of this program be for the average consumer? A: Consumers will have timely access to safer, higher-quality generic drugs. A more efficient regulatory and approval process will maintain FDA's high standards for generic drug products for the public, while increasing the number of available products. Q: Why is the GIVE program necessary? A: Over the last three to four years, the number of abbreviated new drug applications submitted to our office has increased. This has led to a growing list of pending applications. We've made a number of successful process improvements during this time. In fact, the office approved a record number of applications during the past two years. We approved 510 products in 2006, and approved more than 650 in the fiscal year that just ended. But the advancement of medical science and the related increasing cost of health care and disease prevention have caused the role of OGD and its review staff to grow. The number of firms producing generic products and the number of products each firm proposes are growing at an unforeseen pace. The improvements we have made serve to unify and enhance the review process to address the growing workload, and to increase the efficiency of our office's review efforts. Q: How will the goals of GIVE be accomplished? A: GIVE will work by combining our office's various efforts into one harmonized activity to implement process improvements throughout the entire program. The initiative is a review-oriented program that is focused on three main areas: * Mobilizing staff efforts to increase review productivity. * Optimizing the capacity and capability of all assets within OGD, and leveraging wherever possible resources from other FDA components. * Using every avenue possible to recruit, hire and train reviewers for our critical-need areas. FOR MORE INFORMATION VISIT Generic Initiative for Value and Efficiency (GIVE) at http://www.fda.gov/oc/initiatives/advance/generics.html |
---Collaboration focuses on type 1 diabetes and other autoimmune indications--- October 2007. GlaxoSmithKline and Tolerx, Inc. today announced the execution of a worldwide alliance to develop and commercialize otelixizumab (TRX4), a novel humanized anti-CD3 monoclonal antibody that has potential across a broad range of autoimmune and immune-mediated inflammatory diseases, including type 1 diabetes. Otelixizumab has been evaluated in type 1 diabetes in two Phase II studies and in psoriasis in two Phase I studies. In clinical trials, otelixizumab has been shown to preserve the function of insulin-producing beta cells in the pancreas in patients with type 1 diabetes, reducing the amount of administered insulin needed to control blood glucose levels. Under the terms of the agreement, Tolerx will have responsibility for the Phase III clinical programme for type 1 diabetes in the "GSK brings a wealth of experience, expertise, and global resources to this collaboration. The agreement with GSK enables us to operationally leverage Tolerx’s expertise in therapeutic immune regulation, expand the development of otelixizumab in type 1 diabetes and other indications, and capitalize on GSK’s considerable worldwide development, regulatory, and commercialisation infrastructure and experience,” said Dr. Douglas J. Ringler, President and Chief Executive Officer of Tolerx. “Moreover, it provides the infrastructural support required to advance our goal of being first-to-market with otelixizumab in type 1 diabetes. We anticipate the collaboration will allow the potential of this novel therapy to be fully explored globally, not only for the treatment of patients with type 1 diabetes but also for those with autoimmune disorders for which the current standard of care is inadequate.” About type 1 diabetes Diabetes (medically known as diabetes mellitus) is the name given to disorders in which the body has difficulty regulating its blood glucose, or blood sugar levels. There are two major types of diabetes: type 1 and type 2. Type 1, also called juvenile diabetes or insulin-dependent diabetes, is a disorder of the body's immune system. In type 1 diabetes, the pancreas produces little or no insulin as a result of the immune system attacking and destroying the insulin-producing beta cells in the pancreas. Therefore, type 1 diabetes patients require frequent administration of insulin therapy each day to control their blood sugar levels. About otelixizumab Otelixizumab is a monoclonal antibody that binds to a receptor component found on all T cells known as CD3, which is involved in normal T cell signaling. Otelixizumab is designed to block the function of autoreactive T-effector cells that attack the body’s tissues and cause autoimmune disease while inducing a subset of T cells called T-regulatory cells that are thought to protect against T-effector cell damage well after the drug has been eliminated from the body. In a Phase II clinical study of subjects with new-onset type 1 diabetes, otelixizumab demonstrated the potential to preserve the function of insulin-producing beta cells in the pancreas and reduce the amount of administered insulin needed to control blood glucose levels for up to 18 months after only a single six day course of therapy. In the study, residual betacell function was assessed by measuring glucose clamp-induced C-peptide release before and after the administration of glucagon. Otelixizumab administration was associated with transient symptoms of flu-like syndrome and transient Epstein-Barr Virus (EBV) reactivation. Tolerx has completed dose optimisation studies in subjects with type 1 diabetes and psoriasis and has identified a dosing regimen that thus far has significantly reduced or eliminated these side effects while maintaining important biological activity. About GlaxoSmithKline GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline at www.gsk.com. About Tolerx Tolerx is a biopharmaceutical company engaged in the discovery and development of novel therapies to treat patients with immune-mediated diseases. Tolerx currently has two antibodies in clinical development: otelixizumab in type 1 diabetes and psoriasis, and TRX1 in cutaneous lupus erythematosus (CLE). TRX1 is a humanised anti-CD4 antibody that is being developed in collaboration with Genentech, Inc. Tolerx is also engaged in preclinical development of new product candidates that induce immunological tolerance for the treatment of autoimmune diseases and circumvent tolerance for the treatment of cancer or chronic viral diseases. For more information, please visit www.tolerx.com. GlaxoSmithKline forward-looking statements Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSKcautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2006. Source: GSK Press Release |
---Study will compare the VEGF Trap-Eye to Genentech’s ranibizumab (Lucentis®)--- Leverkusen, Germany, and Tarrytown, NY (August 03, 2007) – Bayer HealthCare AG and Regeneron Pharmaceuticals, Inc. announced today that the companies have initiated a Phase 3 study of the VEGF Trap-Eye in the neovascular form of age-related macular degeneration (wet AMD). The study will be a non-inferiority comparison of the VEGF Trap-Eye and ranibizumab (Lucentis®, a registered trademark of Genentech, Inc.), an anti-angiogenic agent approved for use in wet AMD. The study will be conducted pursuant to a Special Protocol Assessment from the U.S. Food and Drug Administration (FDA). This trial, known as VIEW 1 (VEGF Trap: Investigation of Efficacy and safety in Wet age-related macular degeneration), is the first study in the companies’ Phase 3 global development program in wet AMD which is planned to be carried out in the U.S., Europe and other parts of the world. “Age-related macular degeneration continues to be one of the leading causes of blindness in adults, and new therapies are essential to providing optimal patient care,” stated Jeffrey Heier, M.D., a clinical ophthalmologist at Ophthalmic Consultants of Boston and chair of the steering committee for the trial. “The results of early phase studies of VEGF Trap-Eye suggest it has the potential to be a highly efficacious treatment with less frequent administration. If these results are confirmed in Phase 3 trials, it would be important for both patients and physicians and would be a significant advance in the treatment of these patients.” “We will continue in our effort to improve the lives of patients suffering from wet AMD and the initiation of the first Phase 3 study is an important step forward in the development of this investigational therapy”, said Kemal Malik, M.D., Member of the Bayer HealthCare Executive Committee, responsible for Global Development. “Our program is designed to investigate VEGF Trap-Eye’s potential to improve vision in patients with wet AMD with less frequent dosing than every four weeks.“ The randomized, double-masked Phase 3 study, is expected to enroll approximately 1,200 patients in more than 200 centers throughout the The primary endpoint of the study is the proportion of patients treated with the VEGF Trap-Eye who maintain or improve vision at the end of one year, compared to ranibizumab patients. Visual acuity is defined as the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Maintenance of vision is defined as losing fewer than 3 lines (equivalent to 15 letters) on the ETDRS chart. After the first year of treatment, patients will continue to be treated and followed for another year. In an analysis of interim data from the ongoing Phase 2 trial in wet AMD, where patients were treated with the VEGF Trap-Eye either monthly or quarterly, combined data for all patients demonstrated a statistically significant reduction in retinal thickness and improvement in visual acuity after 12 weeks, compared to baseline. There were no drug-related serious adverse events, and treatment with the VEGF Trap-Eye was generally well-tolerated. The most common adverse events were those typically associated with intravitreal injections. The interim results of this Phase 2 trial were presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) this past May. The Companies expect to report final primary endpoint results of the trial at a scientific meeting later this quarter. Bayer HealthCare and Regeneron are collaborating on the global development of the VEGF Trap-Eye for the treatment of wet AMD, diabetic eye diseases, and other eye diseases and disorders. Bayer HealthCare will market the VEGF Trap-Eye outside the About the VEGF Trap-Eye Vascular endothelial growth factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels (angiogenesis) to support the growth of the body’s tissues and organs. It has also been associated with the abnormal growth and fragility of new blood vessels in the eye, which lead to the development of wet AMD. The VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein that binds all forms of VEGF-A along with the related placental growth factor (PlGF). The VEGF Trap-Eye is a specific and highly potent blocker of these growth factors. Blockade of VEGF, which can prevent abnormal blood vessel formation and vascular leak, has proven beneficial in the treatment of wet AMD. Blocking VEGF has been shown to be effective in patients with wet AMD; and a VEGF inhibitor, ranibizumab, has been approved for treatment of patients with this condition. About AMD Age-related macular degeneration (AMD) is a leading cause of acquired blindness. Patients with this condition can experience a loss of vision due to the development of abnormal, fragile blood vessels in the back of the eye. A particular type of AMD, called wet AMD, accounts for approximately 90 percent of AMD-related blindness. Wet AMD is the leading cause of blindness for people over the age of 65 in the About Regeneron Pharmaceuticals Regeneron is a biopharmaceutical company that discovers, develops, and intends to commercialize therapeutic medicines for the treatment of serious medical conditions. Regeneron has therapeutic candidates for the potential treatment of cancer, eye diseases, and inflammatory diseases and has preclinical programs in other diseases and disorders. Additional information about Regeneron and recent news releases are available on Regeneron’s worldwide web site at www.regeneron.com About Bayer HealthCare The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Forward-looking statements This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. |
---Optaflu® to help meet growing need for seasonal influenza vaccines, production technology has potential for quick scale-up in case of an influenza pandemic-- ---Novartis proprietary cell culture technology offers possibility to obtain a better matched vaccine with circulating viruses than currently available technology--- Basel, April 27, 2007 - Novartis has received a positive opinion supporting European Union approval of its cell culture-derived seasonal influenza vaccine Optaflu®, which is aiming to become the first influenza vaccine to utilize a mammalian cell line, rather than chicken eggs, for antigen production. The Committee for Medicinal Products for Human Use (CHMP), which reviews applications for all 27 countries in the EU as well as "Novartis Vaccines is pleased with this positive recommendation for Optaflu, the first cell culture-derived influenza vaccine and the first major innovation in influenza vaccine manufacturing in more than 50 years," said Dr. Jörg Reinhardt, CEO of Novartis Vaccines and Diagnostics. "Optaflu contributes to meeting the growing demand for seasonal influenza vaccines, and this production technology offers the potential for quick scale-up of manufacturing in the event of an influenza pandemic." A submission is anticipated in 2008 for More than 3,400 people received Optaflu during the clinical development program evaluating the vaccine's safety and immunogenicity. Data reviewed by CHMP from the clinical program showed Optaflu fulfilled all of the Committee's immunogenicity criteria. The data further showed the cell culture-derived influenza vaccine was comparable to conventional egg-based vaccines in efficacy and tolerability. Additives, such as antibiotics, are avoided in the Optaflu production process. Additionally, people allergic to eggs and egg products can benefit from receiving this vaccine since it is created without egg proteins. Like established conventional egg-based vaccines, Optaflu is administered via intramuscular injection. Data from the Phase III clincial program were presented at the Influenza Vaccines for the World Congress (IVW) meeting in October 2006. About cell culture technology and the Novartis proprietary cell line Cell culture manufacturing is the first major innovation in influenza vaccine manufacturing in more than 50 years. It represents a new approach to vaccine production whereby influenza virus is propagated in readily available mammalian cell lines rather than in chicken eggs. Virus cultivation utilizing the Novartis proprietary cell line as an exclusive host offers the possibility of more robust virus proliferation since most circulating viral strains are unable to replicate in chicken eggs. In a next generation of products, it also offers the possibility for vaccine seed strain development that more closely matches the original "wild" virus because cell culture technology eliminates the need for passage through eggs where the virus may be forced to adapt in order to replicate. As a result, the antigen included in the vaccine may express more authentically the surface of the wild type virus, potentially translating into a better immunogenic and effective response. The Novartis proprietary cell culture technology enables flexible, faster start-up of vaccine manufacturing. With the advent of this technology, Novartis Vaccines is contributing to meet the growing need for seasonal influenza vaccines and quickly respond to a potential pandemic influenza threat. About influenza and pandemic influenza Influenza can cause mild to severe illness and at times can lead to death. Worldwide, influenza epidemics result in approximately 250,000 to 500,000 deaths each year[1]. Influenza-related complications can include pneumonia and dehydration, and worsening of chronic conditions, such as congestive heart failure, asthma, or diabetes[2]. The World Health Organization (WHO) and its Global Influenza Surveillance Network recommend vaccination as the principal method for preventing influenza[1]. Increased circulation of avian influenza A/H5N1 virus has been documented in Asia and References 1. World Health Organization "Influenza Fact Sheet" http://www.who.int/mediacentre/factsheets/fs211/en/index.html Accessed October 10, 2006 2. Centers for Disease Control and Prevention (CDC) "Questions & Answers: The Disease" http://www.cdc.gov/flu/about/qa/disease.htm Accessed October 10, 2006 Disclaimer This release contains certain forward-looking statements, relating to the Novartis Group's business, which can be identified by the use of forward-looking terminology such as "to help," "potential," "possibility," "aiming to", "recommended", "generally follows the recommendations," "anticipated," "potentially, "can," "could," or similar expressions, or by express or implied discussions regarding potential marketing approvals or future sales of Optaflu. Such forward-looking statements reflect the current views of Novartis regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Optaflu to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Optaflu will be approved for any indications in any market or that Optaflu will reach any particular sales levels. In particular, management's expectations regarding Optaflu could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including additional analysis of existing clinical data and new clinical data; competition in general; the ability of Novartis to obtain or maintain patent or other proprietary intellectual property protection; increased government, industry, and general public pricing pressures; and other risks and factors referred to in the Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis Vaccines and Diagnostics is a division of Novartis focused on the development of preventive treatments and tools. Novartis Vaccines is the world's fifth-largest manufacturer and second-largest supplier of influenza vaccines in the Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative-products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in For more information, please visit http://www.novartis.com |
Market Intelligence and Pharma Data Mininge-Published, Feb 1st, 2007 ICC- Route de Pré Bois 20,
Abstract Biomedical journals have recently published several market analysis covering new drugs and sales data for rheumatoid arthritis, influenza vaccines, monoclonal antibodies and recombinant protein therapeutics derived from commercial databases. This paper will revisit and analyse some of the published sales and market data. Authors from firms selling commercial data bases to pharmaceutical and biotechnology industry present their own market data, sales forecast and identify brands, which will drive future growth and markets. Comparison of the sales figures of blockbuster medicines from company sources and commercial reports and databases reveals significant discrepancies. Three Datamonitor papers in 2006 provide different sales and forecast for influenza vaccines. Comparison data from different sources and projections from previous reports or forecasts with actual data is rarely presented or discussed. Such discrepancies may result in a misleading evaluation of product, markets, portfolio, research development and company. Biomedical publications should develop a new policy and apply the same high standards of data reporting as in regular publications for commercial data sources. Introduction Market intelligence, consultancy and knowledge providers to the pharmaceutical, biotechnology, device and diagnostic industry, had total global sales of $6 billion in 2005. Each year commercial data firms issue hundreds of research reports costing thousands of dollars each and 2007 will be the same. These reports cover global best selling medicines, new drugs and market analysis of selected therapeutic area. It is claimed that these exclusive research reports identify drivers of future growth and market size forecasts that drive decisions and shape strategies by executives. IMS with 2005 sales of $1.8 billion has a 30% market share and its global data, figures, graphs for top selling medicines are extensively covered in several popular news, financial, business, scientific and medical media thereby having a 100-fold multiplier impact factor as a yearly ritual. Similarly Ernst & Young, Accenture, IBM, Boston Consultancy, Price Waterhouse Cooper, Scrip, Reuters, Thompson-ISI and Datamonitor reports are quoted and reported extensively in new and old media. Unlike IMS, other data-mining firms do not report income/sales from pharmaceutical and biotechnology companies. In addition to industry, hedge funds, venture capital, investment funds, industry specific funds, leading banks and traders use these reports and data to make decisions about trade, investment and profits. All major pharmaceutical and biotech companies in the world are customers of such reports and data.
The advantage of these reports is that they provide a comprehensive list of blockbuster drugs, sales and companies involved and market trends. The disadvantages are the high cost of these reports, somewhat outdated data, confidential nature of the data collection and evaluation and divergence of sales figures in comparison with company reports. All commercial databases take shelter behind the safe harbor statement “their models and methodologies for estimation of sales figures may give results which may differ from actual results”. Company annual and quarterly reports and presentations provide easy access to real data for their top selling products. The disadvantage is that some European and Japanese companies still do not provide sales data for their best selling products and use a different financial year than the calendar year. Global Sales Data Forecasting and predicting the future markets and trends for pharmaceuticals and monitoring the actual market sales remains an important tool for the industry to plan its growth, R&D and marketing strategy. Several commercial reports cover global blockbuster drug sales and R&D trends (1-4) (Table 1). Differences of over $1 billion were observed for the top 1-2 brands and 0.5 billion for several brands (1-4) since 2002. The ranking of best selling brands and growth rates were significantly different. Ranking of the companies based on sales of biologic drugs, R&D expenses and R&D budgets was different as well (5-8) (Tables 2, 3). Table 1. Global Pharmaceutical and Biotechnology Market 2005-2006 ($ Billion)
Global Pharmaceutical Market IMS Health 2005 603 Global Biotechnology Market Ernst & Young 2005 63 Datamonitor 40 IMS 52 Leading therapeutic categories in 2005
IMS Top Line Industry Data 2005; Ernst & Young 2006 Beyond Borders Maggon K. R&D Paradigm Shift & billion dollar biologics. In Shayne C. Gad Ed. Handbook of Pharmaceutical Biotechnology. John Wiley, Table 2. Top Companies Sales of Biologics in 2005
Sales as reported by company’s annual results/reports. The IMS figures for 2005 are included if available. TNF Antagonists The market data presented for TNFα antagonists 2005 sales was included in a recent paper (9) covering rheumatoid arthritis drugs and markets published in March 2006. The companies (Amgen, Johnson & Johnson, and Abbott) had released their yearly earnings and top brand sales by last week of January 2006. The paper mentions a total market for the TNFα antagonists as more than $6 billion, the actual figure as reported by companies was $5.5 billion in 2004 and $8.6 billion in 2005 (Enbrel $ 3.7 billion, Remicade $ 3.5 billion, Humira $ 1.4 billion). Combined sales of Enbrel and Remicade are 83% and closer to the 80% of the total TNFα market mentioned in the paper (9). Only one monoclonal antibody in Phase III (Cimzia, UCB) for which NDA has been filed is mentioned. Twenty other monoclonal antibodies in Phase III trials in arthritis patients are not mentioned? The article fails to provide an updated 2005 sales or development status of Phase III/NDA projects in rheumatoid arthritis. There is a real need for a new agent, which in combination with methotrexate and TNFα antagonists will increase sustained response rate without increasing risk of infections or other cardiovascular adverse reactions (10-12). The success of future agents will depend on the real therapeutic gain achieved with $25000 annual cost and the ability of healthcare systems to cover all arthritis patients. Reichert and Pavlou (9) analysis of the monoclonal antibody market in 2004 predicted the monoclonal antibody market to $16.7 billion in 2008, the combined sales of the top selling therapeutic monoclonal antibodies in 2005 were $14 billion as reported by companies. This figure excludes antibodies used for diagnostic tests and procedures. Datamonitor (14-17) projected figures for 2008 were reached in 2006 with sales of $18 billion. The sales figures for Avastin were $ 500 million lower than the actual sales figures reported by Roche for 2005 and for Erbitux higher by $ 140 million. With over 200 companies developing monoclonal antibodies and the total number of active projects in R&D and clinical development at 132 seems to be lower than the real figure (17-20). FDA approved only one monoclonal antibody Orencia in 2005 and two Lucentis and Vectibix in 2006. Influenza Vaccines Two recent 2006 Datamonitor articles on influenza vaccine provide divergent sales and forecast. One article reports 2004 sales of $1.3 billion and a 2010 forecast of $3.7 billion (21), and another $1.1 billion sales and $3.1 billion forecast (22). A news story (23) about Datamonitor Influenza vaccine reports 2005 sales of $1.6 billion and a 2010 forecast of $3.0 billion (Table 4). Concerns about avian influenza and stockpiling by governments and the strong demand for influenza vaccines in 2006 were offset by mild influenza winter resulting in oversupply of the vaccine in Table 4. Influenza Vaccine Sales and Forecast Sales $ billion 2004 2005 2010 forecast Reference --------------------------------------------------------------------------------------------- 1.2 1.8 NA Company* 2005 Annual report Datamonitor Report 2006 1.3 NA 3.7 8 1.1 NA 3.1 9 NA 1.6 3.0 10 ________________________________________________________________ * Sanofi Aventis, Glaxo Smith Kline, Merck, Chiron-Novartis, Solvay, Crucell-Berna, MedImmune Therapeutic Proteins Datamonitor (4, 25, 26) market analysis and forecasting methodology has been described. Once again the global market growth projections for therapeutic proteins from 2004 to 2010 are provided. The market for 2005 was estimated at $40 billion and for 2010 at 50 billion. IMS (1) data gave a figure of $ 52 billion and Ernst & Young (2) of $ 63 billion (Table 1). The sales of the top 20-biotechnology products (20) were $59.6 billion and assuming that these products account for 75% of the total market, the total market value is near $75 billion for 2005. Similar results are obtained if total sales of different therapeutic categories are added (Table 1). The listed brands driving future markets25 and growth missed out on several current blockbuster brand like Synagis, Rituxan, Herceptin, Prevanar, Copaxone, Avastin and blood factors (5). Discussion Variables like exchange rates, bulk discounts, stockpiling, parallel imports, damages/returns and exclusion of certain developing countries cited as contributing factors in data collection by commercial firms may explain small differences of a few million dollars. There is no logical explanation for differences of $500-1000 million in the same year for some best selling global brands or R&D expenses of top research driven companies. Such differences were first reported in 2003 for the year 2002 sales data and have continued (1-4). In the era of Global Accounting Standards and SEC requirements, company-reporting standards are well known and more reliable while commercial data collection methods remain confidential. Commercial firms have failed so far to correct the deficiencies in their methodology and require constant improvements to eliminate and minimize differences. Publications in biomedical journals of such reports as regular or invited features with significant discrepancies, missing data and lack of comparative data require new editorial policy and guidelines. Commercial research reports and sales figures differ significantly in comparison to companies’ annual reports. The data, trends and predictions may significantly impact market value of companies, R&D projects, licensing, merger and acquisition, joint ventures, alliances and deals. Similarly ranking of companies by sales, profitability, R&D budgets, new blockbuster drugs may change market value, perceptions and cost of loans or new funds for companies. Since commercial reports are used for strategic decision-making, it is obvious that significant discrepancies in sales data, market projections may contribute to the market failure of some new drugs and decline in R&D productivity and current low public perception of the pharmaceutical industry. Significant variations in past predictions concerning present trends and markets forecasts have been observed. The data mining firm’s recent data should match or come closer to company’s latest annual reports for top selling global brands, sales growth, R&D budgets and total market size in different indications. Significant and persistent discrepancies in data from different sources will ultimately undermine the current reliance of industry on commercial data and research reports. It is relatively difficult to publish an article challenging big commercial firms. The present article challenges commercial research report figures, marketing and growth forecast and future trends published in selected biomedical journals. Editors of journals when contacted about discrepancies in data decided to ignore the differences and not publish the corrections. One editor decided that an article pointing out data differences was not worth publishing as it did not go beyond discrepancies. When additional comments were added, the editor decided that the article was not balanced and must include positive aspect of commercial research reports. There is no independent comparative evaluation of past predictions and actual results or any oversight by regulators or SEC for commercial reports. In the era of Global Accounting Standards and SEC requirements, company-reporting standards are well known and more reliable while commercial data collection methods remain confidential. The sales projections for the same product for any year should converge for all validated methods for data collection, forecast and analysis. References 1. IMS Top Line Global Industry Data (2005). www.imshealth.com, http://www.ims-global.com/insight/insight.htm 2. Ernst & Young. (2005 & 2006). Global Biotech Report and Global Pharmaceutical Trends. Levinson A.D. (2005). What distinguishes biotech from big pharma? Global Industry Perspectives. 3. Reuters Health. Reports (2004) The Pharmaceutical Market Outlook to 2010. http://www.reutersbusinessinsight.com/content/rbhc0091t.pdf. 4. Datamonitor Potential blockbuster drugs (2004). www.datamonitor.com 5. Gray N. (2006). Changing Landscape The World top 50 Pharmaceutical Companies. Pharmaceutical Exec. 26, 78-101. 6. Maggon K. R&D paradigm shift and billion dollar biologics. In Handbook of Pharmaceutical Biotechnology. Ed Gad, S. C. John Wiley, 7. Maggon K. The ten billion dollar molecule. Pharmaceutical Executive, 23, 60-68, 2003. 8. Maggon K. Best Selling Human Medicines 2002-2004. Drug Discovery Today, 10, 738-742 (2005). 9. Moreland, L.,Bate G. & Kirkpatrick, P. Abatacept. Nature Reviews. 5. 185-186(2006). 10. Sesin, C. A. & Bingham, C. O. Remission in Rheumatoid Arthritis: Wishful Thinking or Clinical Reality? Seminars in Arthritis and Rheumatism, 35, Issue 3, 185-196 (2005). 11. Hochberg, M. C. et al. The Benefit/Risk Profile of TNF-Blocking Agents: Findings of a Consensus Panel. Seminars in Arthritis and Rheumatism, 34, 819-836(2005). 12. Miossec P. Therapeutic targets in rheumatoid arthritis: More to come but which one(s) to select? Drug Discovery Today: Disease Mechanisms, 2, 327-330 (2005). 13. Reichert J. M.& Pavlou A. K. Monoclonal Antibody Market. Nature Reviews 3, 383-384, (2004). 14. Evans, D. & Das, R. Monoclonal Antibodies : evolving into a $ 30 billion market. Datamonitor Report. (2005). 15. Reichert J. M. et al. Monoclonal antibodies success in the clinic. Nature Biotechnology. 23, 1073-1078 (2005). 16. Pavlou, A. K. & Belsey, M. J. The therapeutic antibodies market to 2008 Eur J Pharmaceut Biopharmaceut., 59, 389-396 (2005). 17. Scannes, L.& Branca, M. A. The evolving market for monoclonal antibodies : Facing new opportunities and pitfalls. Pharmaweek 1-23 (2006). http://www.pharmaweek.com/Exclusive_Content/2_23%20test.asp 18. Upping the ante on antibodies. Nature Biotechnology 23, 1065 - 1072 (2005). 19. Liossis, S. N.C. & Tsokos, G. C. Monoclonal antibodies and fusion proteins in medicine. J Allergy Clin Immunol. In Press, Corrected Proof, Available online 20. Qu, Z.et al. Development of humanized antibodies as cancer therapeutics. Methods, 36, 84-95 (2005). 21. Belsey M. J. et al. Influenza Vaccines. Nature Reviews. 5, 183-184, 2006. 22. Belsey M. et al. (2006). Growth Drivers and resistors of the influenza market: The importance of cell culture flu. J. Commerc. Biotechnol. 12, 150-155. 23. Datamonitor report (2006). Pandemic threat reignites influenza vaccine market. Webbolt. 24. Quigley, E.(2006). Influenza therapies: vaccines and antiviral drugs. Drug Discovery Today 11, 478-480. 25. Recombinant protein therapeutics—success rates, market trends and values to 2010. Nature Biotechnology 22, 1513 – 1519 (2004). 26. Pavlou A.K. The immunotherapies markets, 2003–2008 Journal of Commercial Biotechnology, 10, 273-278 (2004). * Please reference or credit any material, article, table or figure cited from http://www.medicineandbiotech.com as: Copyright 2004-2007. MedicineandBiotech.com, http://www.medicineandbiotech.com/ |
By Dr. Krishan Maggon, Ph.D., Pharma Biotech R&D Advisor
Volume 4, November 2004. The withdrawal of rofecoxib (Vioxx) by Merck [1-3] has put pressure over the research based pharmaceutical industry, which is driven by unmet medical needs. The current drug approval system, marketing of drugs, directed consumer advertising, high priced new medicines coupled with the end of the blockbuster drug model, low R&D productivity, increasing costs and generic drugs have collectively put the future growth of the big pharma at risk. Merck has been the dominant R&D driven and most admired company during the 1980s and 1990s and had one of the highest market valuations in the industry. During the past two years, it has lost 55% of the market value including the loss of 40% of market value after rofecoxib news [1-3]. Thus, a sale loss of $2.5 billion of rofecoxib resulted in a loss of $27 billion market value in one day and another $20 billion within the next month. Several analysts had downgraded the stock due to late termination of two R&D projects in Phase III last year, rofecoxib withdrawal, federal, states and SEC investigations, product injury and litigations costs and the patent expiry of Zocor in 2006. Drug stocks of research based companies have lost 5-10% of the market value (total loss $50 billion) due the intense media coverage and concerns about the class cardiotoxicity of all Cycooxygenase II inhibitors (coxibs) [4-7]. Every day since withdrawal of rofecoxib, new class action lawsuits are filed in courts against Merck. Wyeth, Pfizer, and Bayer made provisions of $15 billion for previous withdrawals like Phen-fen (Redux), Glitazone (Rezulin) and Cerivastatin (Baycol) respectively. Analysts have provided estimates of up to $20 billion for rofecoxib litigation. Four selective COX II inhibitors are marketed in Europe and two in USA. Celecoxib (Celebrex) and valdecoxib (Bextra) are approved in the USA, while Parecoxib (Dynastat), Etoricoxib (Arcoxia) and Lumiracoxib (Prexige) are marketed in European countries. Celecoxib was the top selling coxib in 2000 and 2001 with sales of $2 billion and $3 billion, respectively but lost market leadership to rofecoxib in 2002 and 2003 due to better gastrointestinal (GI) tolerance. In the first half of 2004, global sales of COX II inhibitors were: celecoxib $1.5 billion, rofecoxib $1.3 billion, valdecoxib $545 million and etoricoxib $92 million. Celecoxib is expected to reach annual sales of $3 billion in 2004. Worldwide 80-100 million patients have used celecoxib and rofecoxib and 40 million in USA. The history of modern drug regulations is closely linked to the incidence of drug induced injury, organ failure and deaths (Table 1). Each tragedy linked to marketed drugs resulted in increased regulations and additional testing to prevent future episodes with new drugs of the same class (Table 2). The Elixir of Sulfanilamide tragedy resulted in the Food, Drug and Cosmetic Act of 1938. The Thalidomide tragedy in early 1960 resulted in requirements for safety and efficacy testing for drugs in animals and humans. Safety testing includes testing new drugs for adverse effects; for example, can a new chemical entity (NCE) cause birth defects, cancer, organ failure, organ toxicity or some other problem. Willman of The Los Angeles Times was honored with a Pulitzer Prize in 2001 for his investigative reporting of FDA fast track approval and seven deadly drugs in 2000 including Rezulin, Fen-Phen and Duract (bromfenac) [8]. All drug withdrawals are followed by regulatory review of similar drugs to rule out a class effect, additional safety data for marketed drugs and additional requirements for drugs in development. The withdrawal of benoxaprofen resulted in a ten fold increase in number of patients (from 200-400 patient year exposure to 2500-5000 patient year exposure to the study drug) required for newer NSAID (Non Steroidal Anti Inflammatory Drugs) and trials in elderly, hepatic and renal impairment and drug interactions. International guidelines require that for long-term treatment of non-life-threatening conditions, 1500 patients should be treated with the drug: for safety-300-600 treated for at least 6 months, and for efficacy at least 100 for 12 months. FDA has routinely required 200 patients treated for 1 year. Astra Zeneca total patient exposure in clinical trials submitted for approval for rosuvastatin (12,500) was considerably greater than the 2,000-3,000 patients submitted for most of the other marketed statins. Since the withdrawal of troglitazone (Rezulin), no other Peroxisome Proliferator Activator Receptor (PPAR) agonist has been approved because of the concerns about the class carcinogenicity, hepatotoxicity and cardiotoxicity. The published and available clinical data indicates an increased cardiac risk to patients linked to the long term use of rofecoxib [9-11]. Cardiovascular (CV) events linked to Cox-II inhibitors, include heart attack, stroke, high blood pressure, fluid retention and heart failure. After rofecoxib, a winning strategy for a safe and effective anti-inflammatory and analgesic COX-II agent is to reduce GI toxicity and not have any cardiovascular, renal, hepatic, neurological or any other toxicity. Toxicology studies in monkeys, in addition to rodents and dogs may help identifying CV risks early in drug development. Clinical trials to generate data for approval and show reduced GI toxicity and CV safety will require 25,000-30,000 patients with several thousands treated for 2-3 years. This is confirmed by recent FDA stance for additional long term safety data for the approval of etoricoxib and lumiracoxib. This has been the requirement for approvals of some new vaccines and drugs for common cold. The industrial R&D should move away from the twin focused NSAID induced GI toxicity and total COX II inhibition. The optimum COX II inhibition may provide cardiac, hepatic, renal, immunological and CNS safety [12, 13]. The total R&D costs for such a drug will be $1.5 billion over 12-15 years. If successful, the rewards are a blockbuster analgesic drug with potential annual sales of $5 billion. The available data indicates a differentiation of available COX-II inhibitors with respect to GI and CV effects [14]. Etoricoxib (Arcoxia) show reduced GI toxicity without increased CV risk but long term data is not available. Valdecoxib (Bextra), Parecoxib (Dynastat) and Lumiracoxib (Prexige) show reduced GI toxicity with increased CV risk. Rofecoxib showed reduced GI toxicity with increased CV risk. Celecoxib (Celebrex) has a similar GI toxicity as popular NSAIDS but may have a potential cardioprotective effect according to Pfizer but increased CV risk according to its critics. |