Dai­ichi Sankyo 'dis­ap­point­ed' as FDA ex­perts spurn AML drug but vote in fa­vor of rare tu­mor drug

Dai­ichi Sankyo has of­fered up the fresh­est case study of just where the line is drawn on can­cer drugs show­ing in­cre­men­tal — or even ques­tion­able — ben­e­fits, as crit­i­cal in­ter­nal re­views from the FDA trans­lat­ed in­to dif­fer­ing ad­vi­so­ry com­mit­tee opin­ions on two of its pitch­es.

By a 3-8 mar­gin, the on­col­o­gy ex­perts con­vened by the agency shot down the Japan­ese drug­mak­er’s case for its acute myeloid leukemia drug quizar­tinib, hav­ing vot­ed in fa­vor of pex­i­dar­tinib in the morn­ing ses­sion. Pex­i­dar­tinib treats be­nign tu­mors known as symp­to­matic tenosyn­ovial gi­ant cell tu­mor.

De­signed specif­i­cal­ly for FLT3-ITD–pos­i­tive AML, quizar­tinib was her­ald­ed as a sig­nif­i­cant new op­tion for re­frac­to­ry pa­tients who are count­ing their last days. Dai­ichi Sankyo bagged the ty­ro­sine ki­nase in­hibitor in a buy­out of Am­bit Bio­sciences val­ued at $410 mil­lion in 2014. Last Au­gust, the com­pa­ny scored a break­through ther­a­py des­ig­na­tion for it on the back of piv­otal da­ta that showed a 27% over­all sur­vival rate com­pared to 20% in the chemother­a­py arm.

Richard Paz­dur

But ad­comm mem­bers sided with FDA re­view­ers in wor­ry­ing that the re­sults, de­spite be­ing sta­tis­ti­cal­ly sig­nif­i­cant, had to do with im­bal­ances be­tween the drug and chemo co­horts. Com­pared to the chemo arm, the quizar­tinib group had a high­er per­cent­age of pa­tients who went on to re­ceive hematopoi­et­ic stem cell trans­plants, a low­er num­ber of non-treat­ed cas­es, and few­er in­stances of in­com­plete OS da­ta — all point­ing to­ward a po­ten­tial bias.

Richard Paz­dur, the pow­er­ful di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, chimed in at the meet­ing, say­ing he hasn’t come across a re­sult like this in 20 years.

“While we are dis­ap­point­ed by the out­come of to­day’s ODAC vote, we will work close­ly with the FDA as it com­pletes the re­view of our sub­mis­sion,” said An­toine Yver, Dai­ichi Sankyo’s glob­al head of on­col­o­gy R&D.

An­toine Yver

Reg­u­la­tors, who are not oblig­ed to fol­low the ad­comm’s ad­vice but of­ten do, will have un­til Au­gust 25 to de­cide af­ter ex­tend­ing an ear­li­er dead­line to re­view more da­ta. Dai­ichi Sankyo’s loss here could be Astel­las’ and No­var­tis’ gain as they con­tin­ue to carve out a place for Xospa­ta and Ry­dapt, re­spec­tive­ly.

It’s a sharp con­trast with pex­i­dar­tinib, which would be the first non-sur­gi­cal treat­ment for a rare but of­ten de­bil­i­tat­ing con­di­tion in­volv­ing tu­mors in joints and ten­dons.

Here the main con­cern was liv­er tox­i­c­i­ty, a con­cern that had pre­vi­ous­ly cur­tailed en­roll­ment in a Phase III. While ad­comm mem­bers ac­knowl­edged the safe­ty is­sues, the ma­jor­i­ty of them trust­ed a de­cent risk eval­u­a­tion and mit­i­ga­tion strat­e­gy, or REMS, would suf­fi­cient­ly low­er the risks.

Though the FDA al­so raised ques­tions about ef­fi­ca­cy, cit­ing a “high lev­el of miss­ing da­ta at Week 25,” 12 of the ex­perts on the pan­el had no prob­lem en­dors­ing the ben­e­fits over the risks.

“I did not see the lon­gi­tude in the da­ta around 25 weeks and this is why I took more of the con­ser­v­a­tive side,” added one of the 3 who vot­ed no. “I was wor­ried about the ef­fi­ca­cy and qual­i­ty of life da­ta be­yond 25 weeks.”

The PDU­FA date for pex­i­dar­tinib is Au­gust 3.

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.

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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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Biohaven CEO Vlad Coric

Bio­haven turns out a dud in fa­tal neu­rode­gen­er­a­tive dis­ease, cast­ing doubt on drug's chances in ALS

With one migraine drug on the market, Biohaven has gone big with its next phase of growth, targeting major neurodegenerative diseases in Alzheimer’s and ALS. The former effort has already gone up in smoke, and a new failure elsewhere in the pipeline could now bode poorly for the latter.

Biohaven’s verdiperstat failed to outperform placebo in reducing the symptoms of patients with multiple system atrophy (MSA), a rare and fatal neurodegenerative disorder, according to a “focused analysis” of the drug’s Phase III trial in that disease toplined Monday.

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