CDER asks FDA to re­voke Mak­e­na's ac­cel­er­at­ed ap­proval less than a week af­ter AM­AG ac­qui­si­tion

Just a few days af­ter an­nounc­ing it was be­ing ac­quired for near­ly $650 mil­lion, AM­AG Phar­ma­ceu­ti­cals $AM­AG re­ceived some sour news it’s like­ly been ex­pect­ing for a while.

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.

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Charles Baum, Mirati CEO

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