Alzheimer's ad­comm mem­bers ques­tion FDA: How can you use amy­loid as the ba­sis for an ac­cel­er­at­ed ap­proval?

The FDA has not yet pro­vid­ed a per­sua­sive sci­en­tif­ic ba­sis for de­clar­ing be­ta-amy­loid as a rea­son­able sur­ro­gate for an ac­cel­er­at­ed ap­proval, sev­en mem­bers of the ad­comm that re­viewed ad­u­canum­ab and unan­i­mous­ly vot­ed against its ap­proval, wrote Wednes­day in the New Eng­land Jour­nal of Med­i­cine.

Al­though the FDA has re­leased key re­views on the in­ter­nal dis­sent around the agency’s de­ci­sion to OK Bio­gen’s new con­tro­ver­sial Alzheimer’s drug, the ex­perts (three of whom have since re­signed from the ad­comm in protest over the ap­proval) ex­plained how more than two dozen ther­a­pies based on this amy­loid hy­poth­e­sis have un­der­gone late-stage clin­i­cal tri­als, and none have shown mean­ing­ful clin­i­cal ben­e­fit.

Pa­trizia Cavaz­zoni

Top FDA of­fi­cials who signed off on the ap­proval, in­clud­ing neu­ro­science head Bil­ly Dunn and CDER di­rec­tor Pa­trizia Cavaz­zoni, si­mul­ta­ne­ous­ly pub­lished a let­ter to the ed­i­tor of NE­JM on Wednes­day, not­ing they dis­agreed with the ad­comm mem­bers’ as­ser­tion that the ben­e­fit of ad­u­canum­ab is “high­ly un­cer­tain.”

They point­ed to their own JA­MA ed­i­to­r­i­al on the is­sue (Bio­gen’s da­ta has not been pub­lished in a peer-re­viewed jour­nal yet) to ex­plain how “a con­trolled dose–re­sponse clin­i­cal tri­al of ad­u­canum­ab was pos­i­tive for both clin­i­cal end points as­sess­ing men­tal func­tion­ing, and one of the two phase 3 tri­als was strong­ly pos­i­tive, show­ing sta­tis­ti­cal­ly sig­nif­i­cant ef­fects on all four end­points as­sess­ing men­tal and dai­ly life func­tion— stan­dard end points in Alzheimer’s tri­als.”

The first au­thor of the NE­JM per­spec­tive Caleb Alexan­der, pro­fes­sor at Johns Hop­kins Bloomberg School of Pub­lic Health, dis­agreed, telling End­points News that the ev­i­dence speaks for it­self, and that he’s al­ready heard peo­ple mis­stat­ing that the ev­i­dence is clear when it is not. He said the sus­tained pub­lic out­cry push­ing back on the ap­proval is a tes­ta­ment to how ir­reg­u­lar the agency’s de­ci­sion-mak­ing was.

Caleb Alexan­der

“It is hard to rec­on­cile the lack of con­vinc­ing clin­i­cal ben­e­fit across two prospec­tive ran­dom­ized tri­als with this ex­pec­ta­tion of some clin­i­cal ben­e­fit of un­known mag­ni­tude over an un­known pe­ri­od,” Alexan­der and co-au­thors wrote. They al­so not­ed that the “sci­en­tif­i­cal­ly un­jus­ti­fied la­bel” for Aduhelm may lead to bil­lions of dol­lars in un­nec­es­sary Medicare ex­pen­di­tures, even if CMS re­stricts cov­er­age in some way.

Bio­gen yes­ter­day called for a wide NCD on a pub­lic com­ment hear­ing with CMS, as well as ear­li­er pay­er cov­er­age be­fore that de­ci­sion is in the books. When that might hap­pen is un­clear, but some ma­jor med­ical cen­ters like the Cleve­land Clin­ic are de­clin­ing to use Aduhelm and some in­sur­ers are de­clin­ing cov­er­age too.

The ad­comm mem­bers al­so com­mend­ed Janet Wood­cock, in­ter­im FDA com­mis­sion­er, for her de­ci­sion to call for an Of­fice of the In­spec­tor Gen­er­al in­ves­ti­ga­tion, which they said “should be ex­pe­di­tious­ly per­formed, so as to learn how this reg­u­la­to­ry fail­ure oc­curred and to en­sure that it doesn’t oc­cur again.”

Why it Works: Man­u­fac­tur­ing a Vac­cine in a Mul­ti-Prod­uct Fa­cil­i­ty.

COVID-19 launched the pharmaceutical industry to the frontline in the battle against the fast-spreading global pandemic. The goal: distribute a safe, effective vaccine as quickly as possible. Major players in the vaccine market needed to partner with contract development and manufacturing organizations (CDMOs) to achieve the goal of mass vaccine quantities under expedited timelines. With CDMOs stepping up to play a critical role in the vaccine manufacturing process, multi-product CDMO facilities took the spotlight. Partnerships quickly formed as the race to save lives and fight a pandemic was on.

Habib Dable, Acceleron CEO

Days of heat­ed ru­mors cul­mi­nate in a re­port that Ac­celeron is in ad­vanced buy­out talks

Days of frothy rumors about possible M&A discussions at Acceleron were capped late Friday with a Bloomberg report asserting that the biotech company is in advanced talks for an $11 billion buyout deal.

Bloomberg was unable to identify any bidders in the deal, but speculation has been running rampant that the surging value of Acceleron stock had to be the result of leaks around the auction of the company. As of early Monday morning, we’re still awaiting the final word.

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Safe­ty fears force Pfiz­er to change piv­otal DMD gene ther­a­py tri­al pro­to­col

As one of the biggest players in an increasingly packed gene therapy space, Pfizer has taken an early lead over specialists like Sarepta in taking a Duchenne muscular dystrophy (DMD) candidate into late-stage testing. But new safety fears have led Pfizer to scale back that trial, cutting out patients with certain genetic mutations.

Pfizer has amended its enrollment protocol for a Phase III test for gene therapy fordadistrogene movaparvovec in DMD after investigators flagged severe side effects tied to specific mutations, according to a letter the drugmaker sent to Parent Project Muscular Dystrophy, a patient advocacy group.

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Merck CEO Rob Davis

Mer­ck emerges as lead bid­der in po­ten­tial Ac­celeron buy­out with deal pos­si­ble this week — re­port

With rumors swirling about a potential buyout of biotech Acceleron and its lead PAH drug sotatercept, market watchers have been keeping close tabs on industry movers and shakers due up for an expensive bolt-on. According to a new report, it appears Merck may be the one.

Merck is in “advanced talks” on a deal to acquire Cambridge, MA-based Acceleron in what previous reports pegged as a potential $11 billion buyout, the Wall Street Journal reported Monday. A deal could come as early as this week, according to the Journal.

Alexander Lefterov/Endpoints News

The coro­n­avirus vac­cine that the world for­got could still help save it

Back at the beginning of the pandemic — back when we still called the virus “novel” and a single case in Washington state could make headlines — there emerged the story of the coronavirus vaccine that the world forgot.

It was an allegory for our pandemic ill-preparedness. At a time when the world had been caught so flat-footed, there were a pair of scientists who had seen the crisis coming, lab-coated Cassandras with an antidote if only the world had listened sooner.

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Paul Hudson, Sanofi CEO (Cyril Marcilhacy/Bloomberg via Getty Images)

Sanofi calls it quits on mR­NA Covid-19 shots, scrap­ping vac­cine from $3.2B Trans­late Bio buy­out

Sanofi is throwing in the towel on mRNA-based Covid-19 vaccines.

The French drugmaker will halt development on its unmodified mRNA Covid-19 shot despite what it said were positive Phase I/II results, a spokesperson told Endpoints News on Tuesday morning. Sanofi said the reason it’s stopping the Covid-19 mRNA program, developed in partnership with its new $3.2 billion acquisition Translate Bio, is because the market is too crowded.

Brian Hubbard, Anji Pharmacetuticals CEO

Look­ing to rewrite the rules of drug li­cens­ing, start­up An­ji is on the hunt for 'dy­nam­ic eq­ui­ty' joint ven­tures

Licensing is one of the most common ways big drugmakers leverage biotech innovation to drive gains across their pipelines — and the structure of those deals is pretty well established. But one biotech with home bases in China and the US thinks it may have a better way.

On Tuesday, Cambridge-based biotech Anji Pharma closed a $70 million Series B with two late-stage molecules in the fold and a mission to rewrite the rules of drug licensing through what it calls “dynamic equity” deals and a joint venture-heavy game plan. The round was funded in whole by Chinese hedge fund CR Capital.

Con­tract re­search is hav­ing a mo­ment right now. Will M&A splash­es dri­ve the in­dus­try to even greater heights?

Contract research organizations are a fairly mysterious bunch. They’re typically considered the skilled laborers behind big drug development — the stage crews who run the trials behind some of the most (and least) successful data reveals in biopharma history.

But all that is changing.

This year, a couple of huge, out-of-the-blue M&A deals sounded the alarm on just how much money is flying around in this corner of the industry.

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Albert Bourla, Pfizer CEO (John Thys, Pool via AP Images)

Covid-19 roundup: Pfiz­er/BioN­Tech sub­mit vac­cine da­ta to FDA for younger chil­dren; Doc­tors kept pre­scrib­ing hy­drox­y­chloro­quine

Pfizer and BioNTech said Tuesday they submitted to FDA positive data from a Phase II/III trial of their Covid-19 vaccine in children aged 5 to less than 12 years old.

A formal EUA submission for the vaccine in these children is expected to follow “in the coming weeks,” the companies said in a statement.

The trial of 2,268 healthy participants aged 5 to less than 12 years old showed the vaccine was safe and elicited robust neutralizing antibody responses using a two-dose regimen of 10 μg doses, which is one-third the dose that’s administered to adults.