CDER asks FDA to revoke Makena's accelerated approval less than a week after AMAG acquisition
CDER has formally recommended that the FDA revoke the accelerated approval for AMAG’s flagship drug, Makena. The medicine, developed to reduce the risk of preterm birth in women who had previously experienced one, failed to show a clinical benefit in its post-approval confirmatory trial, CDER said in a statement.
“We have concluded that the available evidence does not show Makena is effective for its approved use,” the statement said.
Following the news, AMAG’s stock price sunk about 6% Monday afternoon but rebounded slightly to finish the day down 4.8%.
Despite the recommendation, Makena and its generic copycats will remain on the market until AMAG and other manufacturers decide to remove them or the FDA requires their removal. AMAG and the generic makers may request a public hearing for regulators to further discuss a potential withdrawal.
Late Monday night, AMAG released a statement indicating they are still considering whether or not to initiate this hearing. They have 15 days to let the FDA know if they want to do so.
“We disagree with the FDA’s proposal to withdraw Makena without having the opportunity to meet with them to discuss the generation of additional effectiveness data while preserving access for patients to the only FDA approved treatment option for indicated women,” AMAG CEO Scott Myers said in the statement. “We are reviewing our options, including the opportunity to request an oral hearing, and will respond to the agency within the allotted time.”
Makena was first granted accelerated approval back in 2011 to lower the chances of a second preterm birth, which is defined as delivery of a baby before 37 weeks. In the trial conducted for the drug’s NDA, AMAG showed that 37% of women on Makena delivered prematurely as opposed to 55% on placebo in a surrogate endpoint. The drug also showed statistically significant improvements in proportions of women giving birth at fewer than 35 and 32 weeks.
However, the confirmatory trial needed to show that Makena not only reduced the risk of premature birth but demonstrate it can be helpful for a newborn’s health. The study did not show a difference between Makena and placebo for either the proportion of women delivering before 35 weeks nor the rate at which infants experienced at least one complication from being born prematurely.
Monday’s recommendation may have been in the works for almost a year, as last October an FDA expert panel voted 9-7 to recommend revoking Makena’s accelerated approval. The meeting itself proved difficult in garnering consensus after an emotional conversation about the choices faced by high-risk women desperate to have a safe birth of a healthy baby.
AMAG is used to facing a rocky road though, as the hedge fund Caligan Partners had been engaging in an attempted activist takeover for some time. Following the panel, both AMAG’s CEO and CMO stepped down in short succession and its two drugs not facing FDA scrutiny, Vyleesi and Intrarosa, were sold off. The company also halted development on another drug in their pipeline following a Phase IIb/IIIa readout.
That set up the acquisition by Covis last week for $647 million when accounting for AMAG’s old debt. The main targets for Covis became ciraparantag, a small molecule meant to stop bleeding in patients on anticoagulants, and Feraheme, a drug for iron deficiency anemia.