Eli Lilly & Company's Gemzar recommended by Advisory Committee to FDA for marketing for treatment of Advanced Pancreatic Cancer

Business Wire, July 24, 1995

ROCKVILLE, Md.--(HealthWire)--July 24, 1995--Gemzar(R) (gemcitabine hydrochloride), an investigational drug by Eli Lilly and Company, for the treatment of advanced or metastatic pancreatic cancer, was recommended to be cleared for marketing today by the Oncology Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA). Gemzar is a novel nucleoside analog, which is a compound that mimics a natural building block of DNA.

An estimated 27,000 people in the United States will die of pancreatic cancer in 1995. Pancreatic cancer, which is generally asymptomatic until late in the course of the disease, is among the most difficult cancers to treat and is rarely curable. Currently, less than 10 percent of patients live more than 1 year after diagnosis.

The committee of expert consultants to the FDA made its recommendation after reviewing and evaluating clinical data on the use of Gemzar in patients with advanced or metastatic pancreatic cancer. The committee's recommendations, while not binding, will be considered by the FDA in its final review of the New Drug Application (NDA) submitted by Lilly on Feb. 1, 1995.

"We are pleased to learn of ODAC's recommendation concerning Gemzar. Gemzar is an innovative investigational drug that targets an unmet medical need in the United States," said August M. Watanabe, M.D., a vice president of the company and president of Lilly Research Laboratories. "As the first newly discovered drug recommended for marketing for the treatment of advanced or metastatic pancreatic cancer in several decades, Gemzar offers the potential of providing new hope to pancreatic cancer patients."

"I want to congratulate the company on putting a lot of effort into a very difficult area (clinical benefit endpoints) in a manner that is conservative," said Richard Gelber, PhD, Professor of Pediatrics in the Division of Biostatistics, Dana Farber Cancer Institute, Boston, Ma., and a member of ODAC.

New Endpoint: Clinical Benefit

Because pancreatic cancer is often difficult to diagnose and is diagnosed in advanced stages, traditional means for establishing the activity of a chemotherapy agent, such as the rate of tumor growth or shrinkage, often do not provide a meaningful analysis of a patient's overall health. Recognizing the unique needs associated with caring for pancreatic cancer patients, Lilly has worked with the FDA on a clinical endpoint with which to measure the efficacy of Gemzar and the impact treatment has on patients.

This endpoint, termed "clinical benefit," is designed to quantitatively measure the effect of Gemzar on patients' overall quality of life. The components include the patient's level of pain, need for pain medication, ability to perform daily activities and weight change. Taken together, data on clinical benefit provide researchers with a more complete view of patients' health and quality of life.

"Lilly's innovative clinical endpoints take into account not just a patient's survival time, but the quality of life during that time," explained F. Andrew Dorr, M.D., medical research advisor, Lilly Research Laboratories. "These endpoints illustrate the benefits of drugs that provide improvements in disease-related symptoms and clinical well-being."

Clinical Data on Survival

The committee's decision was based on the presentation of results from two clinical trials. One Phase III, multi-center, randomized trial compared Gemzar to 5 fluorouracil (5-FU). The study measured survival, an overall estimate of clinical benefit and tumor shrinkage in patients who had not previously received chemotherapy.

In this study, 63 patients were treated with each compound. The six month survival rates were 46 percent and 31 percent for Gemzar and 5-FU respectively, and the one-year survival rates were 18 percent and 2 percent for Gemzar and 5-FU respectively. There was an approximately one and a half month improvement in median survival in patients who received Gemzar in this study.

In addition, 24 percent of patients who received Gemzar experienced "clinical benefit" compared with 5 percent of patients treated with 5-FU. The partial response rate (50 percent or greater decrease in tumor size) for patients treated with Gemzar was 5.4 percent compared with 0 patients treated with 5-FU. Disease stabilization (a decrease of less than 50 percent and an increase of less than 25 percent in tumor size) for patients treated with Gemzar was approximately 39 percent compared with 19 percent for patients receiving 5-FU.

"This randomized study showed a 30 percent improvement in median survival, illustrating the potential benefit of Gemzar as the initial treatment for patients with advanced pancreatic cancer," according to lead investigator Malcolm Moore, Princess Margaret Hospital, Ontario, Canada, who presented the results to the committee.

A second Phase II trial included 63 patients who had not responded to 5-FU treatment. Symptoms improved in 27 percent of patients, with a median survival time of 3.85 months, a six month survival rate of 31 percent and a one-year survival rate of 4 percent. A partial response rate was observed in approximately 10 percent of patients, and disease stabilization was reported in approximately 30 percent of patients.