FDA Approves Herceptin for the Adjuvant Treatment of HER2-Positive Node-Positive Breast Cancer

-- Herceptin Significantly Reduced the Risk of Breast Cancer Recurrence by 52 Percent in Pivotal Studies  -- -- Only Targeted Biologic Therapy Approved for Use in Adjuvant and Metastatic HER2-positive Breast Cancer  --     South San Francisco, Calif. --  November 16, 2006 --  Genentech, Inc. (NYSE: DNA) announced today that the U.S. Food and Drug Administration (FDA) approved Herceptin® (Trastuzumab), as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel, for the adjuvant treatment of HER2-positive node-positive breast cancer. Adjuvant therapy is given to women with early-stage (localized) breast cancer who have had initial treatment surgery with or without radiation therapy with the goal of reducing the risk of cancer recurrence and/or the occurrence of metastatic disease.   The FDA approval was based on data from an interim joint analysis of more than 3,500 patients enrolled in two Phase III clinical trials. These results showed that the addition of Herceptin to standard adjuvant therapy significantly reduced the risk of breast cancer recurrence, the primary endpoint of the studies, by 52 percent (or a hazard ratio of 0.48) in women with HER2-positive breast cancer, compared to those patients who received standard adjuvant therapy alone.   "The results of the joint analysis show that, for women with early-stage HER2-positive breast cancer, the addition of Herceptin to chemotherapy reduces the relative risk of breast cancer recurrence by approximately half, which translates into fewer women dying from one of the most aggressive types of breast cancer," said Edward Romond, M.D., Professor of Medicine, Division of Hematology/Oncology at the University of Kentucky. "This is the largest improvement in outcome for any group of women with breast cancer in 25 years."   "Our work with Herceptin exemplifies our commitment to developing the right drug for the right patient. We designed Herceptin for the approximately 25 percent of women whose breast cancers overexpress HER2 because we believed that we could make a significant impact for these patients battling a very aggressive, difficult-to-treat disease," said Susan Desmond-Hellmann, M.D., M.P.H., Genentech's president, product development. "These adjuvant studies showed that, in women with HER2-positive lymph node-positive breast cancer, Herceptin reduces the risk of developing metastatic disease, which could benefit thousands of lives worldwide each year."   "This approval also highlights a first step in a major initiative to conduct studies of Genentech targeted therapies in earlier stages of disease where they have the potential to have the greatest impact," added Desmond-Hellmann.   After three-and-a-half years in the study, 87 percent of women treated with Herceptin plus chemotherapy were disease free, compared to 71 percent of women treated with chemotherapy alone. A survival analysis conducted after patients had been followed for a median of 24 months showed a 33 percent reduction in the risk of death (based on a hazard ratio of 0.67), which is equivalent to a 49 percent improvement in overall survival.   Each study had an independent external Data Monitoring Committee (DMC) that reviewed data from the studies, including cardiac safety data, on a regular basis. According to the investigators, serious or life-threatening (and in rare cases, fatal) cardiac events, most commonly congestive heart failure (weakening of the heart muscle), occurred approximately 3 to 4 percent more often in the Herceptin plus standard therapy arms than in the standard therapy alone arms. Other adverse events reported in both studies included dyspnea and interstitial pneumonitis, which occurred at a rate of less than 1 percent.   "Today's approval is wonderful news for women with early-stage HER2-positive breast cancer and another significant milestone in the Herceptin story," said Fran Visco, president of the National Breast Cancer Coalition. "Thanks to the thousands of breast cancer patients, clinical investigators, the FDA, Genentech and advocates, who have all played critical roles in Herceptin's development, we now have a treatment option that represents a major advance for women with HER2-positive breast cancer before the disease has metastasized. We look forward to continuing our collaboration with Genentech on future Herceptin research."   Additional Background on the Joint Analysis Studies The two Phase III trials were sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the North Central Cancer Treatment Group (NCCTG), in collaboration with the Cancer and Leukemia Group B, the Eastern Cooperative Oncology Group and the Southwest Oncology Group.   These randomized, controlled trials studied four cycles of doxorubicin (adriamycin) and cyclophosphamide followed by paclitaxel, either every three weeks or weekly for 12 weeks, compared with the same regimen plus 52 weeks of Herceptin beginning with the first dose of paclitaxel.   The joint analysis results were first presented at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO) in May 2005 and subsequently published in The New England Journal of Medicine (NEJM) in October 2005.   About Herceptin Herceptin is a targeted therapeutic antibody treatment for women who have tumors that overexpress the human epidermal growth factor receptor 2 (HER2) protein. HER2-positive breast cancer is an especially aggressive form of the disease that affects approximately one-fourth of women with breast cancer. Research has shown that women with HER2-positive breast cancer have a greater likelihood of recurrence, poorer prognosis and decreased survival compared to women with HER2-negative breast cancer. Special testing is required to identify women who have HER2-positive breast cancer and who may be candidates for treatment with Herceptin.   Herceptin is the only targeted biologic therapy approved for treatment of HER2-positive breast cancer in the adjuvant and metastatic settings. Herceptin first received FDA approval in September 1998 for use in women with metastatic breast cancer. In this setting, it is indicated for treatment of patients both as a first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy.   In clinical trials of HER2-positive metastatic breast cancer patients, Herceptin in combination with chemotherapy (paclitaxel) was the first anti-HER2 agent to demonstrate an improvement in survival in a Phase III trial. In December 2001, Genentech received FDA approval to include, in the product label, data that showed an improved median overall survival for women with HER2-positive metastatic breast cancer treated initially with Herceptin and chemotherapy, compared to chemotherapy alone (median 25.1 months compared to 20.3 months).   Herceptin Safety Profile Herceptin administration can result in left ventricular dysfunction and congestive heart failure (CHF). The incidence and severity of left ventricular cardiac dysfunction/CHF were highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens.   Herceptin should be discontinued in patients receiving adjuvant therapy for breast cancer who develop a clinically significant decrease in left ventricular function. In patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function, discontinuation of Herceptin should strongly be considered.   Serious infusion reactions and pulmonary toxicity have occurred; rarely these have been fatal. Discontinuation of Herceptin should be strongly considered for infusion reactions manifesting as anaphylaxis, angioedema, pneumonitis, or acute respiratory distress syndrome.   Exacerbation of chemotherapy-induced neutropenia has also occurred.   The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea (shortness of breath), rash, neutropenia (decrease in the number of neutrophils, a type of white blood cell), anemia, and myalgia (muscle pain).   About Breast Cancer According to the American Cancer Society, 212,920 women in the United States will be diagnosed with breast cancer in 2006, and 40,970 will die from the disease. Excluding skin cancer, breast cancer is the most common form of cancer among women and the second-leading cancer killer among women, after lung cancer. The chance of a woman having invasive breast cancer some time during her life is about 1 in 8. The chance of dying from breast cancer is about 1 in 33. Breast cancer death rates are going down. This decline is probably the result of finding the cancer earlier and improved treatment.   Source: Genentech Press Release

FDA Approves Avastin in Combination With Chemotherapy for First-Line Treatment of Most Common Type of Lung Cancer

-- Avastin Is First Therapy to Extend Survival Beyond One Year in Patients with Advanced Non-Small Cell Lung Cancer  --     -- Genentech Expands Patient Access Programs to Include Annual Expenditure Cap for Avastin  --     South San Francisco, Calif. --  October 11, 2006 --  Genentech, Inc. (NYSE: DNA) announced today that the U.S. Food and Drug Administration (FDA) has approved Avastin® (bevacizumab) to be used in combination with carboplatin and paclitaxel chemotherapy for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC), the most common type of lung cancer. The approval is based on a Phase III study (E4599) that showed Avastin in combination with chemotherapy resulted in a 25 percent improvement in overall survival compared to chemotherapy alone (based on a hazard ratio of 0.80). "Bevacizumab, in combination with chemotherapy, is the first therapy in 10 years to improve on standard first-line treatment for advanced lung cancer and the first FDA-approved therapy ever to extend survival for these patients beyond one year in a large, randomized clinical study," said Alan Sandler, M.D., director of Medical Thoracic Oncology at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., and lead investigator on the E4599 trial. "With this survival benefit, bevacizumab represents an important therapy for many advanced lung cancer patients fighting this difficult disease."   "Lung cancer is responsible for more than one-third of all U.S. cancer deaths, killing more people than breast, prostate, colon, liver and kidney cancers combined," said Laurie Fenton, president of the Lung Cancer Alliance in Washington, D.C. "The approval of Avastin plus chemotherapy is a significant stride in the right direction, and we are pleased that Genentech continues to make lung cancer a priority."   About E4599 The FDA approval for this new indication was based on results from E4599, a randomized, controlled, multi-center trial that enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. Patients with mixed histology were excluded if the predominant cell type was squamous. Results showed that patients receiving Avastin plus paclitaxel and carboplatin chemotherapy had a 25 percent improvement in overall survival, the trial's primary endpoint, compared to patients who received paclitaxel and carboplatin alone (based on a hazard ratio of 0.80). One-year survival was 51 percent in the Avastin plus chemotherapy arm versus 44 percent in the chemotherapy-alone arm. Median survival of patients treated with Avastin plus chemotherapy was 12.3 months, compared to 10.3 months for patients treated with chemotherapy alone.   The E4599 trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, under a Cooperative Research and Development Agreement between NCI and Genentech. The trial was conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).   E4599 Safety Analysis The most common Grade 3-5 (severe) adverse events in Study E4599 seen in Avastin-treated patients were neutropenia (low white blood cell count), fatigue, hypertension (high blood pressure), infection and hemorrhage.   In Study E4599, the rate of pulmonary hemorrhage requiring medical intervention for the paclitaxel and carboplatin plus Avastin arm was 2.3 percent (10/427), compared to 0.5 percent (2/441) for the paclitaxel and carboplatin-alone arm. There were seven deaths due to pulmonary hemorrhage reported by investigators in the paclitaxel and carboplatin-plus Avastin arm, as compared to one in the paclitaxel and carboplatin-alone arm.   In previous clinical experience with Avastin in combination with paclitaxel and carboplatin in NSCLC, patients with a specific type of NSCLC called squamous cell carcinoma had a higher risk of experiencing life-threatening or fatal pulmonary bleeding. Squamous cells are a particular kind of cell that form in the lining of the air ducts in the lung. Because of the risk of bleeding attributed to this population, patients with NSCLC classified as predominantly squamous histology were not included in the E4599 trial.   About the New Avastin Annual Expenditure Cap and Genentech's Access to Care Programs Genentech also announced today that the company plans to initiate a first-of-its-kind program to cap the overall expense of Avastin to $55,000 per year per eligible patient for any FDA-approved indication. The program will be available for eligible patients regardless of whether they are insured. The company plans to launch the new program in January 2007. In addition, the company announced that it has doubled its contribution to independent charities that provide co-pay assistance to a total of $50 million.   "The clinical development program that led to Avastin's three FDA approvals suggested dose and duration vary depending on tumor type," said Arthur D. Levinson, Ph.D., Genentech's chairman and chief executive officer. "The new expenditure cap on Avastin is a step Genentech is taking to address this variability in current and future FDA-approved indications. This new program, along with the increased contribution to independent charities that provide co-pay assistance to patients, continues our 20-year history of commitment to patient access."   The price of Avastin was established in February 2004 upon the FDA approval of the drug for the treatment of first-line colorectal cancer in combination with 5-FU based chemotherapy. At that time, the monthly price of Avastin was set below the standard of care chemotherapy for metastatic colorectal cancer at approximately $4,400.   In advanced lung cancer, a higher dose of Avastin is indicated. This dose was based on clinical data from a randomized dose-ranging Phase II study of Avastin in combination with chemotherapy. Based on this trial, ECOG and NCI selected the higher dose for the pivotal Phase III trial in NSCLC. The typical monthly cost of Avastin at this dose is approximately $8,800 and, based on median progression-free survival as measured in the E4599 trial, the average cost per course of therapy in NSCLC is approximately $56,000.   Avastin is covered by most insurers and Medicare for its approved indications. Genentech's donation to independent co-pay charities helps provide assistance to eligible patients with higher co-pay burdens. For eligible uninsured patients, the Genentech Access to Care Foundation (GATCF) provides Avastin for free.   Genentech has provided more than $850 million in free drug to patients since 1990. In 2005 alone, GATCF supported over 18,000 patients by providing approximately $200 million of free product. To learn more about the GATCF, independent charities that provide co-pay assistance to patients and potential financial assistance options, patients can speak with an Alternative Funding Specialist from Genentech's Single Point of Contact (SPOC) group by calling 888-249-4918 or visiting http://www.SPOConline.com.   About Lung Cancer According to the American Cancer Society, lung cancer is the single largest cause of cancer deaths among men and women in the U.S. and is responsible for nearly 30 percent of cancer deaths in this country. The American Cancer Society estimates that more than 170,000 Americans will be diagnosed with lung cancer this year, and 162,000 Americans will die of the disease this year. NSCLC is the most common type of lung cancer.   About Avastin Avastin, in combination with intravenous 5-fluorouracil (FU)-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum; and in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC). For full prescribing information and boxed warnings on Avastin and information about angiogenesis, visit http://www.gene.com. For more information on Avastin, visit http://www.avastin.com.   The FDA first approved Avastin on February 26, 2004, as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. The National Comprehensive Cancer Network recommends Avastin plus chemotherapy as a standard treatment for the first- and second-line treatment of metastatic colorectal cancer and as a first-line treatment of advanced non-squamous NSCLC.   Avastin Safety The most serious adverse events associated with Avastin across all trials were gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common adverse events in patients receiving Avastin were asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria.   About the Avastin Development Program Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a broad development program for Avastin that currently includes 130 clinical trials across 25 different types of cancer. Avastin is being evaluated in Phase III clinical trials for its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, non-small cell lung, prostate and ovarian cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in a variety of solid tumor cancers and hematologic malignancies. For further information about Avastin clinical trials, please call 888-662-6728.   About VEGF and Tumor Angiogenesis Genentech is a leader in research and product development in the area of angiogenesis, the process by which new blood vessels are formed. The link between angiogenesis and cancer growth has been discussed by many researchers for decades; however it was not until 1989 that a key growth factor influencing the process, vascular endothelial growth factor (VEGF), was discovered by Napoleone Ferrara, M.D., a staff scientist at Genentech. Ferrara and his team at Genentech cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Ferrara then created a mouse antibody to this protein.   In 1993, in a study published in the journal Nature, Ferrara and his team demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play an important role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997.

EXCLUSIVE FEATURE OUTSOURCING CLINICAL TRIALS: THE NEW DNA OF THE PHARMA INDUSTRY

by Kishore Jethanandani, MA (Economics), MBA Business Editor- MedicineandBiotech.com, bus_editor@medicineandbiotech.com A new biotech century, with the promise of a rich crop of new drugs, has arrived. Right? Wrong. Bad news abounds in the R&D world of bio-tech these days. The yield of successful new products continues to decline, costs of development of each drug are increasing and rates of returns from the successful drugs are plummeting. At the root of the problem is the archetypal pharmaceutical firm which does all its research, development, manufacturing and marketing in-house. In the new biotech century, the industry will be fragmented with increasing number of firms specializing in one or two levels of the value chain. Despite the surging progress in the biomedical sciences, the new drugs submitted for approval have steadily declined. According to statistics quoted by the FDA, the number of new molecule entities declined from 70 in 1993 to a low of 25 in 2003 (1). The old model of commercializing new products in the pharmaceutical industry is broken. The costs of developing new products have zoomed from an average of $300 million to over $800 million (2). Bain and Company, a management consulting company, factored in the cost of failed drugs and estimated that the costs of drug development rose from $1.1 billion per drug in the second half of the 1990s to $1.8 million in the new millennium corresponding to a decline in the success rate from 14% to 8% (3). Almost the entire increase in costs was accounted for by higher costs of clinical trials. One such horror story is of Pfizer which lost $2 billion as a result of failures in liver toxicity (4). In the past, pharmaceutical companies conducted their own research and development as well as clinical trials. The testing methods were uncomplicated with clinical trials were carried out on animals before human trials were conducted. Increasingly, this method of clinical trials is unable to predict with any degree of accuracy the outcomes on human beings. A recent report by the FDA sums the problem as " the current drug discovery process, based as it is on in vitro screening techniques and animal models of (often) poorly understood clinical relevance, is fundamentally unable to identify candidates with a high probability of effectiveness. The current scientific understanding of both physiology and pathophysiologic processes is of necessity reductionistic (e.g., is knowledge at the gene, gene expression or pathway level) and does not constitute knowledge at the level of the systems biology of the cell, organ, or whole organism, and certainly does not reach a systems understanding of the pathophysiology of particular diseases. Reaching a more systemic and dynamic understanding of human disease will require major additional scientific efforts as well as significant advances in bioinformatics (5). The new vision for product development will have recourse to data mining techniques to develop predictive models for improving the success rate of new drugs. "Examples of tools that are urgently needed include better predictors of human immune responses to foreign antigens, methods to further enhance the safety of transplanted human tissues, new techniques for assessing drug liver toxicity, methods to identify gene therapy risks based on assessment of gene insertional and promotional events, and efficient protocols for qualifying biomaterials" (6), according to a recent paper published by FDA. This implies an array of skills in toxicology, bioinformatics and data management and biological knowledge that no drug company can ever dream of acquiring without raising costs to astronomical level. Increasingly, the industry will be fragmented. Clinical trials are increasingly conducted by CROs alone. According to the research conducted by Life Science Insight, the number of companies who are leveraging or considering the option of leveraging the expertise of CROs is 60% (7). Progressively, the vendors are learning to specialize in techniques and diseases to differentiate themselves from numerous others in the industry. The process of outsourcing of clinical trials to CROs is expected to accelerate in the near term future. "The major regulatory change facilitating outsourcing of clinical trials was 21 CFR 11. 21 CFR 11 put guidelines in place for collecting trial data electronically, enabling companies to have more control over data and get data in house more quickly, even when studies are conducted overseas", according to Judy Hanover, Research Analyst, Life Science Insights. Outsourcing to companies overseas has also become attractive as "Offshore trials give sponsors access to treatment-naive subject populations large enough so that companies can do the kind of enrichment and use the study designs they need to get results, while minimizing enrollment-based delays. Operating costs are also lower, making offshore trials, especially in countries like India that increasingly have standards approximating US GCP guidelines", Judy Hanover added. While the risk of loss of intellectual property does exist, it can be controlled by CROs within their precincts. "With increased use of the internet, rising numbers of "chat" and "blog" settings where trial subjects compare their experiences with the drugs they are taking, present a growing risk to confidentiality". Judy Hanover observed. In offshore locations, there is the added perceived risk that companies may not follow the strict standards that American companies adopt. Respected companies such as Biocon in India have taken their own initiatives to assuage such fears. "In an effort to emphasize the company's core policy of transparency, Biocon took the unprecedented initiative to become the first Pharma Company in India to share clinical trial data on its website (July 30, 2004)", a company representative responded to a questionnaire. This was done following a public interest law-suit filed by a non-profit group in India. The increasing specialization in the industry is expected to lower costs, speed up product development and lower the rates of failures. "CROs have considerably improved the processes involved in clinical trials", Ellen Julian, Director, Research, Life Science Insights, an IDC company, summed up. According to a recently completed study of the Life Science Insights, "the percentage of respondents (in its survey), conducting no clinical trial process redesign is expected to fall from 39% to 29% in 2004. The percentage of respondents planning a significant amount of process redesign is expected to rise from 12% to 22% in 2004". The most important reasons attributed to investment in process redesign, according to the Life Science Insight Insights, was reducing the time and cost of trials while improving the quality of the research (8). The birth pangs of the brave new world of biotech innovations need the entrepreneurs to act as the mid-wives of the new era in product development. A demise of the monolithic pharmaceutical companies will signal that a new age in biotech has arrived. Challenge and Opportunity on the Critical Path to New Medical Products. FDA, March 2004 Tufts Centre for the Study of Drug Development "Rebuilding Big Pharma’s Business Model’ by Jim Gilbert, Preston Henske and Ashish Singh, Business and Medicine Report, November 2003 Rotman, D, "Can Pfizer Deliver?" Technology Review, February 2004 Challenge and Opportunity on the Critical Path to New Medical Products. FDA, March 2004 FDA, Op cit "Today’s CRO: Understanding Changing Requirements for Clinical Trials Outsourcing, July 2004, IDC. IDC, op cit *Please reference or credit any material, article or figure cited from http://www.medicineandbiotech.com as: Copyright 2004. MedicineandBiotech.com, http://www.medicineandbiotech.com/ Disclaimer: MedicineandBiotech.com is managed by AstraGen LLC. Please re-distribute this e-magazine. AstraGen LLC and MedicineandBiotech.com do not assume, and hereby disclaim, any liability for any loss or damage caused by errors or omissions in any material published at the web-site http://www.medicineandbiotech.com, whether such errors or omissions resulted from negligence, misstatements or other oversights.

ABC's of Clinical Trials By: Neerja Sethi, Ph.D. Biotech and Pharmaceutical companies conduct clinical trials to prove efficacy and safety of drugs before releasing the therapeutics into the market. A clinical trial (also clinical research) is a research study in human volunteers to answer specific health questions. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people and ways to improve health. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. Thousands of chemicals, both synthetic and extracted from "natural" sources, are being examined in the hope of finding new drugs with which to combat human and veterinary diseases. The first step is to use laboratory tests to find if these substances have a significant effect on, for example: cells growing in tissue culture laboratory animals such as rats and mice If the drug achieves the desired effect in laboratory animals, without killing them in the process, the drug developer applies to the U. S. Food and Drug Administration for an IND, an investigational new drug application. Granting of an IND allows testing in humans to begin. This occurs in three phases. Phase I- A small group (20–100) of healthy volunteers is given the drug to see: if it is safe how quickly it is absorbed, metabolized, and excreted from the body Phase II-A group (up to several hundred) of volunteer patients with the disease are given the drug to see: how effective it is against the signs and symptoms of the disease what side effects may occur Phase III-Hundreds to thousands of patients with the disease are given the drug to get more reliable data on its: effectiveness safety best dose rare side effects all compared with the drug(s) that are currently used for the disease. If all goes well, the drug manufacturer applies to the Food and Drug Administration for an NDA, a new drug application. If it is granted, the generic name of the drug is replaced by a brand name chosen by the manufacturer. For example, one of the first drugs used against AIDS was azidodideoxythymidine (AZT). When placed on the market, this name was replaced by the brand name zidovudine. Phase IV trials-post marketing studies delineate additional information including the drug's risks, benefits, and optimal use. Even after a drug is available for prescription, its use is carefully monitored and unexpected side effects are reported. Some Basic Terminology TREATMENT IND: IND stands for Investigational New Drug application, which is part of the process to get approval from the FDA for marketing a new prescription drug in the U.S. It makes promising new drugs available to desperately ill participants as early in the drug development process as possible. Treatment INDs are made available to participants before general marketing begins, typically during Phase III studies. To be considered for a treatment IND a participant cannot be eligible to be in the definitive clinical trial. TREATMENT TRIALS: Refers to trials which test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy. PREVENTION TRIALS: Refers to trials to find better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes. DIAGNOSTIC TRIALS: Refers to trials that are are conducted to find better tests or procedures for diagnosing a particular disease or condition. Diagnostic trials usually include people who have signs or symptoms of the disease or condition being studied. SCREENING TRIALS: Refers to trials which test the best way to detect certain diseases or health conditions. QUALITY OF LIFE TRIALS (or Supportive Care trials): Refers to trials that explore ways to improve comfort and quality of life for individuals with a chronic illness.

An Outline of the Drug Development Process NOTE: Drug Development involves a complex, FDA-regulated process of clinical trials. In every subsequent issue of MedicineandBiotech.com, we will discuss and describe different procedures involved in Clinical Trials-Editor. By Dr. Neerja Sethi, Ph.D. Food and Drug Administration (FDA)-approved drug development process for one drug can extend from 6-12 years and can cost as much as $30 million to $1 billion dollars! The discovery phase or the pre-clinical phase can cost $3-5 million. During this phase, the in vitro and in vivo (animal) testing is performed to determine the efficacy, safety and any toxic side-effects of the drug. If promising results are obtained, the scale-up conditions for the Chemistry, Manufacturing and Controls (CMC) are set-up to manufacture the drug according to Good Manufacturing Practice (GMP) regulations. Following this, the Investigational New Drug (IND) application is filed for FDA approval before progressing to Phase I clinical trials. At this stage, the success of a drug can be rated at 10%. After the approval of IND, the drug’s safety and efficacy are tested in different sub-set of population in different doses, formulations, parameters, etc. during 3 distinct phases of clinical trials; Phase I, Phase II and Phase III. This period of clinical trials can range from 6-9 years and cost $25 million to $80 million dollars. The probability of success of a drug with good results at this stage is 65%. The results obtained, during the Phase I, II and III trials, are compiled for a New Drug Application (NDA) at this stage for FDA approval. This is a very critical step and the total process involves pre-NDA meetings with FDA, preparation, submission of NDA, followed by the review process by the FDA. There is a 75% possibility of success at this stage. FDA approval can extend from 1-3 years. The FDA approval allows the drug to be marketed, after the revisions, restrictions and other suggestions by the FDA are implemented. These steps are outlined in the figure above and show the time-span of the complete drug development process, which can extend from 6-9 years till the final approval by the FDA.