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Regulatory Focus™ > News Articles > 2020 > 10 > FDA seeks withdrawal of Makena, generics from market

FDA seeks withdrawal of Makena, generics from market

Posted 05 October 2020 | By Michael Mezher 

FDA seeks withdrawal of Makena, generics from market

The US Food and Drug Administration (FDA) on Monday proposed to withdraw Amag Pharmaceuticals’ preterm birth drug Makena (hydroxyprogesterone caproate injection) and its generics from the market after a postmarket study failed to confirm clinical benefit.
The request comes nearly a year after FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee recommended that the agency withdraw its approval for the drug and more than nine years after it received accelerated approval. (RELATED: Makena withdrawal? A look at the timeline and other accelerated approvals, Regulatory Focus 1 November 2019).
FDA granted accelerated approval to Makena in early 2011 with its approval contingent on the completion of a clinical trial and clinical follow-up study of women who participated in the trial, initially due in 2016 and 2018, respectively. Both deadlines were later delayed by two years.
In March 2019, Amag, which acquired Makena in 2014, announced that the trial did not demonstrate a statistically significant benefit over a placebo in reducing preterm delivery or neonatal morbidity and mortality.
The announcement triggered FDA to convene its advisory committee to review evidence related to the drug and make a recommendation on whether the agency should withdraw Makena from the market or allow it to remain on the market, with or without a new confirmatory trial. In a 9-7 vote, the committee recommended FDA pursue withdrawal of the drug.
At this stage in the process, FDA has sent a notice of opportunity for a hearing (NOOH) to Amag and the five companies that hold abbreviated new drug applications (ANDAs) for generic versions of the drug to provide Amag a chance to request a hearing and the generic manufacturers an opportunity to submit comments about the proposed withdrawal.
To request a hearing, Amag must file a written request within 15 days of receipt of the notice or it will waive the opportunity. If the company does request a hearing, it has 30 days to provide “data, information, and analyses to demonstrate that there is a genuine and substantial issue of material fact that requires a hearing.”
For now, Makena and its generics will remain on the market until either their manufacturers voluntarily withdraw them or FDA requires their removal.
FDA explains that it has “legal authority to use expedited procedures to withdraw approval of a product that has received an accelerated approval if, among other reasons, ‘a study required to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit of the product fails to verify and describe such effect or benefit,’  or ‘other evidence demonstrates that the product is not safe or effective under the conditions of use.’” The agency also notes that it has the authority to withdraw an ANDA when the listed drug it references is withdrawn for different reasons described in sections 505(e) or 505(j)(6) of the Federal Food, Drug, and Cosmetic Act or when the reference listed drug was withdrawn for reasons related to safety and effectiveness.
FDA, Letter

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