To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Gemzar Cleared by FDA for Pancreatic Cancer URL: http://www.pslgroup.com/dg/8CD2.htm Doctor's Guide May 16, 1996
INDIANAPOLIS, May 16, 1996 -- The United States Food and Drug Administration has granted Eli Lilly and Company permission to market Gemzar(R) for the treatment of locally advanced or metastatic pancreatic cancer, a usually fatal disease that will strike about 26,000 Americans this year. The FDA cleared Gemzar for marketing after evaluating results of two clinical studies involving the new drug, a nucleoside analogue that mimics a natural building block of DNA. Gemzar improved median survival in people with advanced and metastatic pancreatic cancer, as demonstrated by statistically significant data from a study comparing Gemzar with 5-Fluorouracil (5-FU), which has been the most common treatment of pancreatic cancer. A second study followed patients treated with Gemzar who had previously been treated with 5-FU. In designing clinical trials for Gemzar, Lilly developed a new and unique clinical endpoint, clinical benefit response, to objectively assess the effect of Gemzar on measured disease-related symptoms. In both clinical trials, approximately one-quarter of patients treated with Gemzar demonstrated improvement in these symptoms. New Hope for Patients "As the first new treatment for pancreatic cancer in several decades, Gemzar represents hope for patients and a breakthrough for Lilly scientists," said August M. Watanabe, M.D., a vice president of the company and president of Lilly Research Laboratories. "The unique Gemzar study design, involving clinical benefit response, demonstrates the company's ongoing commitment to innovative research and development in oncology." Pancreatic cancer, one of the most difficult cancers to treat, is hard to detect because patients remain asymptomatic until late in the course of the disease. Currently, less than 10 percent of all pancreatic cancer patients live more than one year after diagnosis. An estimated 26,000 people in the U.S. will be diagnosed with pancreatic cancer in 1996. Given the difficulty in diagnosing pancreatic cancer, traditional means for establishing the activity of a chemotherapy agent, such as the rate of tumor growth or shrinkage, often cannot provide a useful measurement of a drug's effectiveness. Recognizing the unique needs associated with caring for pancreatic cancer patients, Lilly designed a clinical endpoint that would provide an objective, quantitative measurement of Gemzar's effect on several important disease-related symptoms experienced by patients. Clinical benefit response is a measure of symptomatic improvement based on 1) level of pain 2) consumption of pain medication 3) ability to perform daily activities and 4) weight change. Patients were considered to be clinical benefit responders only if they experienced improvement in at least one measurement without deterioration in any of the others; this improvement must have reached an established level for at least four consecutive weeks. "With a disease like pancreatic cancer, it's important to take a patient's survival time into account," explained F. Andrew Dorr, M.D., medical research advisor, Lilly Research Laboratories. "With clinical benefit response, we are able to demonstrate the benefits of drugs that provide improvements in certain disease-related symptoms, in addition to increasing survival time, for some patients." Gemzar Clinical Data The FDA reviewed two pivotal Gemzar clinical trials in granting permission for marketing: one trial compared Gemzar with 5-FU in patients who had not previously received chemotherapy, and another involved patients who had previously been treated with 5-FU. The Phase III study of Gemzar involved 126 pancreatic cancer patients -- 63 of these patients received Gemzar therapy and the other 63 patients received treatment with 5-FU. Of these patients, more than 70 percent entered the study with metastatic disease, the most advanced stage of pancreatic cancer. Gemzar demonstrated a statistically significant advantage in survival over 5-FU; Gemzar patients had a 5.7 month median survival as compared with 4.2 months for 5-FU patients. From this trial, the six-month probability estimate for survival of patients treated with Gemzar is 46 percent (30 patients), compared with 29 percent (19 patients) for 5-FU patients. After one year, the survival probability estimate was 18 percent (9 patients) for Gemzar patients, compared with two percent (2 patients) for 5-FU patients. (Survival probability estimates take results from the clinical trial and, using a mathematical equation, generalize them to the larger population of pancreatic cancer patients.) "Although the improvement in median survival was only 1.5 months, this translates into a relative improvement in median survival of about 36 percent, reflecting the very lethal nature of this disease. It's really the combination of an improvement in survival, a decrease in certain tumor-related symptoms, and usually manageable side effects that make Gemzar such an attractive and welcomed new treatment for patients with pancreatic cancer," said investigator Mace L. Rothenberg, M.D., University of Texas Health Science Center, San Antonio, Texas. This study also demonstrated that 24 percent of previously untreated patients who received Gemzar experienced a clinical benefit response, compared with five percent of patients treated with 5-FU. This difference also is statistically significant. A Phase II trial of Gemzar, conducted among 63 patients who had previously been treated with 5-FU, showed a median survival time of 3.9 months. In this trial, 87 percent of patients entered the study with metastatic disease. Of these patients, 31 percent survived for six months, and four percent survived for one year. In addition, clinical benefit response was observed in 27 percent of patients. Gemzar's side effects were generally manageable with less than one percent of patients discontinuing their therapy for any of the following side effects. A decrease in some infection-fighting white blood cells, called neutropenia, was observed in 63 percent of patients, with moderate to severe decreases in 25 percent of patients. This effect on the blood was the most frequent reason for reducing or limiting the dose of Gemzar. Common adverse events in clinical trials included nausea and vomiting (69 percent), fever (41 percent), edema or fluid retention (up to 34 percent), rash (30 percent) and flu-like symptoms (19 percent). Only about 10 percent of all patients participating in Gemzar clinical trials discontinued therapy due to side effects. Hair loss, usually minimal, was reported in 15 percent of patients. This side effect was reversible, and none of the patients experienced complete hair loss from their Gemzar treatment. Lilly: An Ongoing Commitment to Oncology Cancer is one of five therapeutic areas in which Lilly is focusing its research efforts. Additional Lilly initiatives in this therapeutic area include a global strategic alliance entered into last year with Seragen Inc. to develop and market fusion toxins as cancer therapy. Also in 1994, Lilly participated in the discovery and isolation of BRCA1, a gene that indicates susceptibility to develop breast and ovarian cancers. Prior to granting Lilly permission to market Gemzar, FDA authorized the company to make Gemzar available in the U.S. through a Treatment Investigational New Drug (IND) program. More than 2,900 pancreatic cancer patients have been treated with Gemzar free of charge since February 1995 as part of this program. Treatment IND status is granted to promising investigational drugs for the treatment of patients with serious or life-threatening illnesses when there is no comparable or satisfactory drug or other therapy available. On July 24 of last year, FDA's Oncology Drug Advisory Committee (ODAC) recommended that the Agency clear the drug for marketing. The New Drug Application for Gemzar was filed with the FDA on February 1, 1995. Lilly has received permission from regulatory authorities in Austria, Brazil, Germany, Hungary, Lithuania, Russia and Sweden to market the drug for treatment of locally advanced or metastatic pancreatic cancer. The company also has received permission from regulatory authorities in Argentina, Australia, Austria, Brazil, the Czech Republic, Finland, Greece, Hungary, India, Italy, Lithuania, Luxembourg, the Netherlands, Russia, South Africa, Spain and the United Kingdom to market the drug for other types of cancer. Gemzar is indicated only for the treatment of pancreatic cancer in the United States at this time. Gemzar is also being studied in other types of cancer. Lilly is a global research-based pharmaceutical corporation headquartered in Indianapolis, Ind., dedicated to creating superior health care solutions -- combining pharmaceutical innovation, existing pharmaceutical technology, disease prevention and management and information technologies -- in order to provide customers worldwide with optimal clinical and economic outcomes. Gemzar(R) (gemcitabine HCl, Lilly) --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.