In the prepublication of the Federal Register (here) which will publish on May 15, 2023, the FDA announced that Makena (Hydroxyprogesterone Caproate injection) will be removed from the Orange Book (OB) along with eight (8) generic applications that referenced Makena as the RLD in its application.

Makena was originally approved in 2011 under the accelerate approval provisions of FDCA  and was ultimately found to lack substantial evidence of effectiveness. “The Commissioner of Food and Drugs (the Commissioner) and the Chief Scientist jointly issued the decision following an October 2022 public hearing” and now this FR notice closes the book on the product (see previous post here). The FR notice states “[A]s a condition of MAKENA’s approval, the sponsor was required to complete a postmarketing trial to verify and describe the clinical benefit of MAKENA in reducing neonatal morbidity and mortality from complications of PTB among babies born to women with a singleton pregnancy who had a previous singleton sPTB. This postmarketing confirmatory trial, Trial 003, failed to show that MAKENA reduced the risk of neonatal morbidity and mortality from complications of PTB and failed to show a treatment effect of MAKENA on the intermediate clinical endpoint that was the basis of MAKENA’s approval”. The history of the events leading to the FDA’s decision are also outlined in the notice.

Because the reference listed drug was withdrawn for lack of efficacy, “FDA will not accept or approve ANDAs that reference MAKENA.”