- A group of experts convened by the Food and Drug Administration voted on Tuesday to recommend the agency withdraw approval for Amag Pharmaceutical's Makena, a drug cleared eight years ago to reduce the risk of premature births. Shares plummeted nearly 30% Wednesday morning.
- The negative vote, which took some analysts by surprise, raises the possibility the FDA might take the rare step of pulling Makena from market. Advisory committee votes aren't binding and the agency is not required to follow the recommendations, though it usually does.
- While the committee generally agreed clinical evidence didn't prove Makena's effectiveness, members were more split on whether approval of the hormonal therapy should be withdrawn. Seven of the 16 panel experts favored the FDA requiring a new confirmatory study, but permitting the drug to remain commercially available.
Makena was initially cleared by the FDA under accelerated approval following positive data from one study of 463 pregnant women.
That OK was conditional on Amag carrying out a confirmatory trial to affirm Makena's effectiveness in reducing the rate of preterm delivery, as well as assess whether treatment lowered neonatal mortality or morbidity.
Results from that study, disclosed in March, were decisively negative, showing no difference between Makena and placebo on either measure.
In theory, a failed confirmatory study would make the FDA's case to withdraw an accelerated approval clear. Practically, however, the agency has a tougher decision to make.
Removing Makena's approval would mean the drug, which competes with four approved generics, could no longer be obtained via FDA-approved manufacturers. Instead, physicians and patients might turn to compounding pharmacies for the progestin-based therapy — the status quo prior to Makena's 2011 approval.
Ken Cacciatore, an analyst at the investment bank Cowen, believes FDA concerns over non-compliant compounding played a role in the agency's decision to clear Makena in the first place.
"If the agency were to decide to now remove the product, clinicians and patients would likely continue to want to use the product, and therefore would be forced to once again source the product through the much less regulated compounding pharmacies," he wrote in an Oct. 29 investor note, arguing the FDA will opt against withdrawing Makena entirely.
Others aren't so sure.
Christopher Raymond of Piper Jaffray views Makena as a test of the FDA's accelerated approval program, writing Wednesday that the agency will want to signal that failure in a confirmatory study carries consequences.
"Barring any Woodcock/eteplirsen-like intervention, we think FDA withdraws marketing authorization," noted Raymond, referring to the director of the FDA's Center for Drug Evaluation and Research, who controversially backed accelerated approval of the muscular dystrophy therapy Exondys 51.
For its part, Amag said it would comment in more detail during an upcoming earnings presentation, scheduled for Nov. 1.
"We are disappointed with the nearly split vote on this key question and we are committed to working with the FDA to identify feasible ways to generate additional efficacy data on Makena while retaining current access to the therapy for at-risk pregnant women," said Amag's Chief Medical Officer Julie Krop in a statement.
Amag added that Makena's use is still supported by the American College of Obstetricians and Gynecologists as well as the Society for Maternal-Fetal Medicine, despite the recent negative results.