Accelerated Approval: Midodrine Experience Shows Regulatory Challenge US FDA Faces With Makena

The orthostatic hypotension treatment midodrine has been on the market for more than 20 years despite the failure of postmarketing studies to confirm clinical benefit; an advisory committee soon will weigh the future of AMAG’s preterm birth drug Makena, which failed its confirmatory trial required as a condition of accelerated approval.

Fuzzy man walking on hanging bridge vanishing in fog. Focus on middle of bridge
The future is uncertain for accelerated approval drugs that fail their confirmatory trials. • Source: Shutterstock

Unresolved questions about the clinical efficacy of a hypotension drug that received accelerated approval 23 years ago highlight the challenges the US Food and Drug Administration and its external advisors will face in weighing whether AMAG Pharmaceuticals Inc.'s preterm birth drug Makena should remain on the market despite failure to confirm clinical benefit.

On 29 October, the FDA will convene its Bone, Reproductive and Urologic Drugs Advisory Committee to consider the continued availability of Makena (hydroxyprogesterone caproate injection, also known as 17P), an accelerated approval drug for which the required confirmatory trial failed to demonstrate a statistically significant treatment difference on two co-primary endpoints

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