When the FDA ap­proved AM­AG Phar­ma­ceu­ti­cals’ fe­male li­bido drug, Vyleesi, months ago sans an ad­vi­so­ry com­mit­tee de­spite weak da­ta — con­tro­ver­sy en­sued. But the Mass­a­chu­setts-based drug­mak­er must now con­tend with the reg­u­la­to­ry fall­out of an­oth­er one of its women’s health drugs: Mak­e­na.

Mak­e­na — which has been on the mar­ket for years as a ther­a­py de­signed to cut the risk of preterm birth in preg­nant women — ear­li­er this year failed a post-con­fir­ma­to­ry study. Now, the FDA has set up a meet­ing of in­de­pen­dent ad­vi­sors in Oc­to­ber to fig­ure out whether or not to take it off the shelves.

For long the ther­a­py, a man-made ver­sion of the hor­mone prog­es­terone, was used off-la­bel sourced from un­reg­u­lat­ed con­coc­tions pre­pared by com­pound­ing phar­ma­cies. Even­tu­al­ly, the FDA grant­ed the prod­uct ac­cel­er­at­ed ap­proval in 2011, de­spite lim­it­ed clin­i­cal da­ta. The man­u­fac­tur­er was ac­quired by AM­AG in 2014. Last year, a pre­filled au­to-in­jec­tor ver­sion with a thin­ner, al­most in­vis­i­ble, nee­dle (ver­sus the orig­i­nal bulky in­tra­mus­cu­lar Mak­e­na in­jec­tion) was en­dorsed by the US reg­u­la­tor.

In March, AM­AG $AM­AG re­vealed the ther­a­py had fiz­zled in the 1,700-pa­tient post-ap­proval PRO­LONG study — blam­ing the fail­ure on the fact that 75% of the pa­tients en­rolled were not from the Unit­ed States, sug­gest­ing that the dif­fer­ence in de­mo­graph­ics had played a role in the set­back.

Back when the FDA orig­i­nal­ly ap­proved Mak­e­na, the agency was “pre­sent­ed with a very dif­fi­cult choice: ac­cept fair­ly lim­it­ed clin­i­cal da­ta (al­beit via spon­sor­ship from the NIH) or con­tin­ue to al­low preg­nant women to re­ceive an in­jec­tion from un­reg­u­lat­ed sources. The Agency clear­ly ac­cept­ed the lim­it­ed clin­i­cal da­ta and grant­ed ap­proval for Mak­e­na as we be­lieve (and spec­u­late) that the true goal was to bring the man­u­fac­tur­ing un­der FDA com­pli­ance,” Cowen’s Ken Cac­cia­tore wrote in a note.

“For these rea­sons, we do not be­lieve that the Agency would now rel­e­gate clin­i­cians and pa­tients to once again sourc­ing this crit­i­cal care prod­uct from un­ap­proved man­u­fac­tur­ing sources.”

As part of its sec­ond-quar­ter re­sults un­veiled in Au­gust, AM­AG said that gener­ic com­pe­ti­tion for Mak­e­na was eat­ing in­to sales, that it had faced sup­ply con­straints re­lat­ing to the prod­uct, that it had de­cid­ed to ex­it the in­tra­mus­cu­lar Mak­e­na mar­ket, and that it had ter­mi­nat­ed an arrange­ment with Pras­co, its au­tho­rized gener­ic part­ner.

Mean­while, AM­AG is bat­tling on oth­er fronts. On Mon­day, the com­pa­ny put out a state­ment ad­mon­ish­ing the ac­tivist hedge fund Cali­gan Part­ners, which has been ac­cu­mu­lat­ing its shares.

“(L)ast month Cali­gan ini­ti­at­ed what ap­pears to be a rushed, ag­gres­sive and mis­lead­ing scheme to seize near con­trol of your AM­AG Board. Now you are es­sen­tial­ly be­ing asked by Cali­gan — as part of a rarely used cor­po­rate ac­tion called a con­sent so­lic­i­ta­tion — to re­move and re­place four mem­bers of the re­cent­ly-re­elect­ed Board as a pre­cur­sor to risky and ill-in­formed changes that Cali­gan wants to make at AM­AG,” the com­pa­ny wrote in a let­ter to share­hold­ers, urg­ing them to dis­re­gard Cali­gan’s cam­paign.

Last month, the com­pa­ny low­ered its full-year fi­nan­cial guid­ance af­ter ex­it­ing the Mak­e­na in­tra­mus­cu­lar mar­ket and re­vis­ing its ex­pec­ta­tions of cira­paran­tag de­vel­op­ment mile­stone rev­enue. Now, the drug­mak­er ex­pects $325 – $355 mil­lion in rev­enue, ver­sus its pre­vi­ous range of $365 – $415 mil­lion.

So­cial im­age: Wes­t­i­form

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.