FDA panel throws dirt on Bristol-Myers' orphan drug metreleptin

Bristol-Myers Squibb's ($BMY) rare disease treatment metreleptin isn't up to snuff for its desired indication, an FDA committee voted, but agency advisers believe the drug shows some promise in a small subset of patients, giving the drug giant some hope for approval.

Bristol-Myers, along with partner AstraZeneca ($AZN), is angling to get metreleptin approved to treat patients with metabolic disorders associated with partial lipodystrophy (LD), a potentially deadly condition that robs patients of the essential hormone leptin and affects a few thousand people around the globe.

FDA advisers, however, were less than impressed with BMS's data for that indication, voting 10-2 that metreleptin's benefits didn't outweigh its risks for patients with partial LD and metabolic ailments like hypertriglyceridemia and diabetes. Instead, the panel voted 11-1 in favor of the drug in patients with generalized LD--a complete loss of leptin--recommending the drug for a narrow slice of an already tiny patient population.

Metreleptin is scheduled for a final FDA decision by Feb. 24, and while the agency isn't required to follow the votes of its advisers, it generally does.

Bristol-Myers and AstraZeneca, however, aren't giving up, and the companies said in a joint statement that they plan to push forward with their hoped-for indication, promising to "work with the FDA to identify the appropriate patients with partial LD who may benefit from metreleptin." Whether that means launching new trials for the drug is unclear, and a Bristol-Myers spokeswoman said only that the company is "exploring all options" in the run-up to its PDUFA date.

And further study may well be necessary thanks to metreleptin's NIH-helmed supporting trials, which did not include a control arm. As FDA staff noted before the panel vote, that quirk makes it difficult to discern whether patient outcomes could be credited to the drug and not improved diet or better compliance with other lipid-lowering treatments. Furthermore, Bristol-Myers is missing a bunch of data on therapy duration, background treatments and protocol changes in its pivotal studies, the FDA said, casting further doubts on metreleptin's odds of swaying regulators.

Bristol-Myers picked up the drug in its $5.3 billion deal for Amylin last year, and the metreleptin program is part of the drugmaker's diabetes partnership with AstraZeneca. Separately, the pair is headed back to the FDA with the once-rejected dapagliflozin, a diabetes drug troubled by cancer risks.

- read the statement