Amgen announces leptin causes weight loss in humans and plans for two Phase 2 trials.

THOUSAND OAKS, Calif.--(BUSINESS WIRE)--June 16, 1997--Following a review of early, preliminary data from the first human trial of leptin, Amgen (NASDAQ:AMGN) Monday announced that it will begin Phase 2 clinical trials to further evaluate the safety and efficacy of leptin in treating obesity.

Amgen said that it has concluded from these early data that there was a dose range at which leptin had an acceptable safety profile and induced weight loss. Amgen also confirmed that it will soon begin a previously planned Phase 2 safety and efficacy trial of leptin in obese patients with Type II diabetes.

"We are very encouraged with these early results," said Gordon Binder, chairman and chief executive officer. "These weight loss and safety data encourage us to move on to Phase 2 testing of leptin both for weight reduction in obese patients and for those obese patients with the form of diabetes known as non-insulin dependent diabetes mellitus or NIDDM. Both of these conditions are major health care problems for Americans."

The preliminary analysis indicated a dose range in which leptin appeared to be safe and reasonably well tolerated in most subjects. At higher doses, injection site reactions and multiple daily injections exceeded the level of acceptability for many subjects. Dose ranges will be further evaluated in the Phase 2 trials.

The most common adverse event was mild to moderate injection site reactions. There were no systemic toxicities detected at any dose. Development of antibodies was noted at higher doses in some patients, but they were not neutralizing and did not appear to be clinically significant.

The randomized, placebo-controlled trial, in which leptin was administered subcutaneously, was conducted at multiple North American sites. The analysis evaluated the data from 165 male and female subjects across a variety of weight categories with no other medical complications. Study subjects were randomized to receive either leptin or placebo. All subjects were given exercise and nutrition counseling.

Although not designed to demonstrate efficacy, this study did provide limited information on the utility of leptin. Some subjects lost weight at all dose levels. The amount of weight loss was highly variable, and there was a "placebo effect," meaning that due to the dietary and exercise counseling provided to both subjects receiving leptin and those receiving placebo, even subjects not receiving leptin lost weight.

For all subjects who completed 28 days on study, 19 percent who received placebo had lost at least 2 kilograms (approximately 4 pounds), and 30 percent to 45 percent of subjects treated with doses of leptin to be used in future studies lost at least 2 kilograms. For the 30 obese subjects who remained on the study for 90 days and who were on doses being studied in Phase 2, the subjects treated with placebo achieved a mean weight loss of 1.5 kilograms (approximately 3 pounds), while those receiving doses that Amgen will take forward to the Phase 2 trials lost a mean of 2 to 4 kilograms (approximately 4 to 9 pounds).

In planned Phase 2 trials, the benefits of one or more daily, subcutaneous injections of leptin will be evaluated. The goal of the trials is to confirm safety and further define tolerable and efficacious doses.

To address the possible lack of patient acceptance of leptin at higher doses, in 1996, Amgen began development of two second-generation alternate leptin molecules. It is expected that one or both of these molecules will reduce injection site reaction and permit delivery of higher doses in more tolerable ways. Extensive preclinical work has been completed for one of these alternative molecules, and it is expected that an Investigational New Drug (IND) application will be filed for it. The other molecule is at an earlier stage of development.

In recent years, obesity has emerged as a major public health issue because it is strongly linked to serious diseases such as NIDDM, hypertension, digestive disorders, a variety of cardiovascular ailments and certain forms of cancer. It is estimated that as many as one in three Americans is clinically obese (at least 20 percent above ideal weight). As a result, obesity contributes to an increased risk of mortality and exacts a high economic cost, estimated at more than $40 billion annually in the United States.

Leptin is a recombinant form of the natural human protein produced by the obese (ob) gene and is made in fat cells. It is thought that leptin helps regulate body fat deposition and, as a result, produces weight loss through effects on metabolism and appetite.

In announcing these early, preliminary data, Amgen cautioned that additional studies will be required before any of the conclusions from the first study can be confirmed.

This news release contains forward-looking statements that involve risks and uncertainties, including risks associated with clinical development and other risks described from time to time in SEC reports filed by Amgen.

Amgen is a global biotechnology company that discovers, develops, manufactures and markets human therapeutics based on advances in cellular and molecular biology.

EDITOR'S NOTE: An electronic version of this news release may be accessed via Amgen's Web site at www.Amgen.com . Visit the Corporate Center and click on Amgen News. Journalists and media representatives may sign up to receive all news releases electronically at time of announcement by filling out a short form in the Amgen News section of the Web site.

CONTACT: Amgen, Thousand Oaks

David Kaye, 805/447-6692 (media)

Denise Powell, 805/447-4346 (investors)