FDA ex­perts gun down Alk­er­mes’ pitch for ALKS-5461, slam­ming the com­pa­ny on mul­ti­ple fronts

A large group of out­side ex­perts at the FDA has slapped down Alk­er­mes’ cam­paign to gain an ap­proval for their de­pres­sion drug ALKS-5461, ob­ject­ing to a messy set of da­ta and the way the biotech man­aged the study and re­port­ed the da­ta.

The key ques­tion: Did Alk­er­mes present sub­stan­tial ev­i­dence of the drug’s ef­fi­ca­cy? Twen­ty pan­el mem­bers vot­ed no, with on­ly 3 yes votes, which makes it ex­treme­ly un­like­ly that the FDA’s for­mal de­ci­sion would be any dif­fer­ent. 

A slight ma­jor­i­ty, 13 to 10, vot­ed that the re­searchers had ad­e­quate­ly char­ac­ter­ized the safe­ty of the drug. But that won’t save this drug. By 21 to 2 the com­mit­tee con­clud­ed that Alk­er­mes had failed to sup­port a fa­vor­able ben­e­fit/risk pro­file.

Alk­er­mes’ stock dropped about 9% in af­ter-mar­ket trad­ing Thurs­day.

The FDA’s harsh re­view drew some at­ten­tion from an­a­lysts, in­clud­ing Stifel’s Paul Mat­teis, who not­ed:

It was al­most as if the FDA was so blunt­ly neg­a­tive in its re­marks so as to fos­ter a pan­el vote that cor­rob­o­rat­ed its skep­ti­cal view­point. ALKS is con­duct­ing an­oth­er tri­al for ‘5461 (but re­sults are a ways away) ahead of a 1/31/19 PDU­FA; the fo­cus for the stock is like­ly to shift to ALKS3831.

The set­back like­ly leaves Alk­er­mes back where it was at the be­gin­ning of the reg­u­la­to­ry process, when the FDA ini­tial­ly re­fused to file the ap­pli­ca­tion and then did an about face and opened the door to a re­view. The com­pa­ny has an­oth­er tri­al un­der­way, but now may well be look­ing at a re­quire­ment to mount new, ex­pen­sive and lengthy clin­i­cal tri­als that would like­ly take at least 3 years to com­plete.

Ever­core ISI’s Umer Raf­fat just shook his head at the time­line.

Tech­ni­cal­ly, ALKS has an­oth­er 450 pt Ph 3 on­go­ing on this drug … which re­ports in 2021 as per clin­i­cal­tri­als.gov.  (I sin­cere­ly hope that ALKS is us­ing MADRS-10 at fi­nal time­point in this tri­al … un­like the last Ph 3).  So sure, there’s a chance … but the con­ver­sa­tion has to move past this drug now.

In its pre­sen­ta­tions to­day, agency rep­re­sen­ta­tives high­light­ed the role of a sin­gle “su­per re­spon­der” in in­flu­enc­ing the out­come of one of the tri­als. Late tri­al de­sign changes al­so drew flak. And Alk­er­mes’ in­sis­tence on craft­ing its own ef­fi­ca­cy mea­sures, leav­ing out key points like sui­ci­dal think­ing, was a dis­as­ter.

Here are some of the blunt ex­pert com­ments from to­day:

“I don’t think there’s ev­i­dence this drug works.”

“I’m very con­cerned about the last minute changes.”

“A sin­gle sub­ject dri­ves the re­sults so strong­ly.”

I’m con­cerned about the “lack of trans­paren­cy about in­di­vid­ual sub­ject lev­el da­ta.”

One pan­elist ob­ject­ed to Alk­er­mes’ “cher­ry pick­ing” study da­ta.

“I think there were too many changes along the way.”

“We pay the ul­ti­mate price be­cause we’re the guinea pigs.”

“A lot more needs to be done.”

Alk­er­mes CEO Richard Pops has been tout­ing this drug for years, build­ing its pro­file as a ma­jor new en­try in the field. But Alk­er­mes comes out of this now with its cred­i­bil­i­ty and rep­u­ta­tion for com­pe­tence tar­nished and its pro­jec­tions on fu­ture growth in ques­tion.

Im­age: Richard Pops at an End­points News break­fast event in San Fran­cis­co Jan­u­ary 2017 End­points News

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

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Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

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