Bristol drug for fat disorder may work, but risky -FDA staff

By Ransdell Pierson

Dec 9 (Reuters) - An experimental Bristol-Myers drug to treat rare and potentially fatal disorders involving loss of body fat appears effective for some patients although with considerable safety risks, staff members of the U.S. Food and Drug Administration said on Monday.

The staff observations were posted on the FDA Website ahead of a planned meeting on Wednesday by a panel of medical experts, who will advise the FDA on the drug, called metreleptin.

The briefing document, meant to flag potential safety concerns about the drug, noted it has been tested since 2000 by the U.S. National Institutes of Health.

Bristol-Myers, which has commercial rights to the medicine, is awaiting U.S. approval for metreleptin, to treat diabetes and/or lipodystrophy, a group of rare acquired or inherited disorders associated with loss of body fat.

Only a few thousand people worldwide are believed to have the disorders, in which fat builds up in the blood and organs such as liver and muscle, and can lead to diabetes, pancreatitis and fatty liver disease. There are no approved drugs to treat underlying causes of the disease, including deficiencies of the human hormone leptin that occur with loss of fat tissue under the skin.

Metreleptin is a form of leptin meant to reduce accumulation of fat in organs, and thereby better control blood sugar and high levels of triglyercides - a type of fat in the bloodstream. Bristol-Myers is developing it in partnership with AstraZeneca (Berlin: ZEG.BE - news) Plc.

The FDA briefing document noted that all patients in the NIH trial received metreleptin, and there was no separate group receiving placebos.

Without a placebo group, it is "challenging to attribute beneficial changes to metreleptin" versus improvements in diet or improved compliance in taking other medicines, the document said.

"Nevertheless, a subgroup of patients appears to have achieved benefits from metreleptin that would be unlikely to have been achieved spontaneously," the report said, including normalization of metabolic control. Benefits were most apparent in patients who had uncontrolled diabetes.

Safety of the drug is hard to gauge, the report said, given the array of medical problems that patients with the disorders already have and the possibility that metreleptin may worsen certain conditions.

It cited concerns about potentially higher risks of lymphoma, immune-related reactions, hypoglycemia, pancreatitis and liver abnormalities.

"It is important to ensure that the appropriate patient population is targeted, given the serious risks that may be associated with the drug," the briefing report said.