Following a controversy over Covis’ preterm birth drug Makena in the U.S. last year, the European Medicines Agency (EMA) is cracking down on hydroxyprogesterone caproate therapies across the pond. This time, the drugs’ questionable efficacy isn’t the only issue at stake.
The EMA’s safety arm, the Pharmacovigilance Risk Assessment Committee (PRAC), on Friday called for the marketing suspension of drugs containing 17-hydroxyprogesterone caproate (17-OHPC) in Europe, citing both safety and efficacy concerns.
The drugs, which go by the names Lentogest and Proluton, among others, are authorized as injections in some European Union (EU) countries to help prevent pregnancy loss or premature birth in pregnant women. They’re also used to treat various gynecological and fertility disorders, including those caused by a lack of the hormone progesterone.
Problem is, aside from limited data on the drugs’ clinical worth in preventing premature birth and other indications, 17-OHPC-based medicines pose a “possible but unconfirmed risk of cancer” in unborn children, PRAC said.
The decision comes about five months after PRAC started its investigation into hydroxyprogesterone drugs. To reach its conclusion, the committee leveraged results from a large population-based study assessing the risk of cancer in people exposed to 17-OHPC over a period of about 50 years from the time they were born.
While the study did flag a potential increase in cancer risk, PRAC caveated that the total number of cancer cases presented was low and that the study suffered from certain limitations.
But aside from the potential safety risk, PRAC also weighed efficacy data, which included results from a study of more than 1,700 women that found 17-OHPC is “no more effective than placebo” in preventing recurrent premature birth or medical complications due to prematurity in newborns.
As part of its probe, PRAC also consulted experts in obstetrics, gynecology and fertility treatment, as well as patient representatives.
The European rebuke comes after Covis’ hydroxyprogesterone caproate injection, known as Makena, faced its own post-approval regulatory review.
Last March, Covis agreed to pull Makena off the market in the wake of a failed confirmatory trial and two FDA advisory committee snubs. In April 2023, the FDA took things a step further by formally revoking the medicine’s accelerated approval. The U.S. regulator did not flag any safety concerns when it announced its approval withdrawal.
Makena was originally approved for pregnant women with a history of spontaneous preterm birth under the FDA’s accelerated pathway in 2011. The drug reached peak sales of $387 million in 2017 and was acquired by Covis in its $647 million buyout of AMAG Pharmaceuticals in 2020.