- The Food and Drug Administration on Monday said the only drug approved to prevent preterm birth hasn't been shown to be effective and should be removed from the market.
- Agency regulators set the process in motion with an Oct. 5 proposal for withdrawal of Makena, which is sold by AMAG Pharmaceuticals. The company has 15 days to respond and has the right to request a hearing before any action is taken.
- AMAG CEO Scott Myers said the company disagrees with the FDA's proposal for removal before it has had the chance to discuss the possibility of another study to prove Makena's effectiveness. A key trial released in March 2019 — designed as a confirmatory study after an initial accelerated approval — found no difference between Makena and a placebo.
Removal of a medicine cleared after an accelerated approval would be a highly unusual step, but it is the way the process is supposed to work. The FDA grants quick clearance to medicines that fill an unmet need, while requiring additional data to further prove safety and effectiveness.
In this case, the FDA approved Makena in 2011 based on a study that showed it could help prevent preterm birth in women who had previously had an unexplained preterm birth, defined as delivery before 37 weeks. The agency then required AMAG to show the medicine could actually improve the health of babies, the ultimate goal of reducing preterm birth.
The confirmatory study not only failed to show a clinical benefit for newborns, it also failed to show that Makena reduced the risk of preterm birth, the FDA said. The agency's notification also went to companies that have approved generic versions of the drug.
AMAG is now evaluating its "full range of potential options," the company said. If it decides to ask for a hearing, the process could take months. That would mean Makena and approved generics would stay on the market until a final decision from the FDA after the hearing.
Taken together, clinical trials support the benefits of Makena, AMAG said. At the time the company released the confirmatory study, AMAG said the demographics of patients were very different than in the initial trial and, in its statement Monday, the company cited an expert as saying the latest trial didn't work because it didn't have enough patients with a high enough risk for preterm birth.
The FDA's move to withdraw Makena comes at a delicate time for AMAG. Just days ago, Covis Group agreed to buy the company for about $650 million including debt. AMAG said it still expects that deal to close in November 2020.
"We would be shocked if Covis had not contemplated this possibility," Piper Sandler analyst Christopher Raymond wrote in a note to investors. The outlook for Makena was already dim after the confirmatory study failed and an FDA advisory panel voted in favor of withdrawal last year, he wrote.
If AMAG tries to draw out the process, it may get another year or so on the market but "the handwriting is on the wall," Raymond wrote. Piper Sandler expects the company to get no revenue from Makena after the fourth quarter of 2021.
While the process of withdrawing a medicine's accelerated approval is unusual, it isn't unheard of.
In 2011, the FDA revoked a breast cancer indication for Roche's blockbuster Avastin medicine, saying it had not been shown to be safe and effective. And last year, Eli Lilly moved to withdraw its cancer treatment Lartruvo after a confirmatory trial failed.