Em­bat­tled AM­AG braces for Oc­to­ber FDA Mak­e­na ad­com, but it need not wor­ry — an­a­lyst

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

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

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Chris Anzalone, Arrowhead CEO

Take­da, Ar­row­head spot­light da­ta from small tri­al show­ing RNAi works in a rare liv­er con­di­tion

Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

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No stranger to gene ther­a­py woes, Astel­las runs in­to an­oth­er safe­ty-re­lat­ed clin­i­cal hold

Astellas Pharma, which has been at the forefront of uncovering the risks associated with gene therapies delivered by adeno-associated viruses, must take another safety alarm head-on.

The FDA has slapped a clinical hold on Astellas’ Phase I/II trial of a gene therapy candidate for late-onset Pompe disease, after investigators flagged a serious case of peripheral sensory neuropathy.

It marks the latest in a streak of setbacks Astellas has encountered since making a splashy entry into the gene therapy space with its $3 billion buyout of Audentes. But the lead program, AT132 for the treatment of X-linked myotubular myopathy (XLMTM), had to be halted more than once after a total of four patients died in the trial — and the scientific community still doesn’t have all the answers of what caused the deaths.

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Albert Bourla, Pfizer CEO (Gian Ehrenzeller/Keystone via AP Images)

Up­dat­ing the Covid-19 vac­cine: FDA of­fers a qual­i­fied thumbs-up ahead of ad­comm

The FDA’s adcomm of outside vaccine experts will meet tomorrow to discuss how to protect the US from a likely coming wave of Omicron cases in the fall and winter, and whether to deploy vaccines that specifically target the Omicron variant.

While the data so far are limited, the FDA sounded an upbeat tone in the briefing documents on Pfizer/BioNTech’s candidates, released this weekend ahead of the VRBPAC meeting.

Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

As court case looms, Bris­tol My­ers touts la­bel ex­pan­sion for Breyanzi

As Bristol Myers Squibb braces for a court battle over a costly delay — at least for Celgene shareholders — for its CAR-T lymphoma treatment Breyanzi, the pharma giant is touting a label expansion in the second-line setting.

Breyanzi, also known as liso-cel, snagged a win on Friday in adults with large B-cell lymphoma (LBCL) who: don’t respond to chemotherapy, or relapse within 12 months; don’t respond or relapse after 12 months; or are not eligible for hematopoietic stem cell transplant after chemo due to their age or comorbidities.

A Mer­ck part­ner is sucked in­to the fi­nan­cial quag­mire as key lender calls in a note

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.