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

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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