Pfiz­er ax­es a key Duchenne MD pro­gram af­ter PhII flop, rais­ing new doubts for a drug cat­e­go­ry that at­tract­ed Roche and Bio­gen

Pfiz­er is jet­ti­son­ing an­oth­er dis­ap­point­ing drug that’s been in the clin­ic for Duchenne mus­cu­lar dy­s­tro­phy. The phar­ma gi­ant says it’s ax­ing work on do­ma­grozum­ab (PF-06252616) — rais­ing the odds against one R&D fo­cus in the field that has at­tract­ed some mar­quee play­ers around the world.

The drug is one of sev­er­al de­signed to in­hib­it myo­statin, which flopped against a one-year test of mus­cle strength, fail­ing to help pa­tients to any sig­nif­i­cant de­gree. By sup­press­ing myo­statin, which blunts mus­cles, the the­o­ry is that a prop­er ther­a­py can help slow the mus­cle-wast­ing ail­ment that in­evitably proves fa­tal to the boys who in­her­it this dis­ease.

Seng Cheng

The fail­ure elim­i­nates one of sev­er­al an­ti-myo­statin ther­a­pies, in­clud­ing BMS-986089, a drug which Bris­tol-My­ers sold to Roche in the spring of 2017 for $170 mil­lion in cash and $205 mil­lion in mile­stones. That drug — now called RG6206 (RO7239361) — is in a Phase II/III study.

Just a month ago Bio­gen al­so got in­to the myo­statin game, pay­ing $27 mil­lion in cash to grab a Phase Ia drug called ALG-801 (BI­IB110) and a pre­clin­i­cal drug ALG-802 from Alive­G­en. Bio­gen not­ed at the time that the two drugs “rep­re­sent nov­el ways of tar­get­ing the myo­statin path­way, which is one of the most thor­ough­ly stud­ied ap­proach­es for mus­cle en­hance­ment.” These ther­a­pies are de­signed to tar­get the nys­tatin path­way, which Bio­gen be­lieves could work bet­ter than oth­er drugs in the clin­ic.

There’s noth­ing un­usu­al about fail­ure in this field, though, where Duchenne MD has proven a tough ob­jec­tive. No­var­tis ex­pe­ri­enced a late-stage set­back with their myo­statin drug bima­grum­ab (BYM338) in 2016. Atara–an Am­gen ($AMGN) spin­off–saw its clin­i­cal can­di­date PIN­TA 745 fail a Phase II study for pro­tein en­er­gy wast­ing in pa­tients with end-stage re­nal dis­ease, forc­ing the biotech to halt de­vel­op­ment ef­forts and switch fo­cus to can­cer. Back in 2011, Ac­celeron ($XL­RN) and Shire ($SH­PG) al­so halt­ed clin­i­cal work on ACE-031, an­oth­er myo­statin drug with big dreams in fight­ing mus­cle wast­ing, then de­cid­ed to scrap it al­to­geth­er in 2013 af­ter run­ning some ad­di­tion­al pre­clin­i­cal tests.

It’s just as bad in oth­er re­lat­ed mus­cle drug fields. Two months ago shares of Sum­mit were crushed in the wake of their failed Phase II for a utrophin mod­u­la­tor, ezutro­mid.

Duchenne MD has al­so been a mine field of con­tro­ver­sy in R&D. Sarep­ta gained an ap­proval for eteplirsen, with­out con­vinc­ing reg­u­la­tors it ac­tu­al­ly works. Now the biotech has been shift­ing at­ten­tion to its gene ther­a­py — put on hold re­cent­ly due to im­pu­ri­ties found in a third-par­ty pro­vid­ed plas­mid — which has looked promis­ing at the very ear­li­est stages of track­ing pa­tient re­spons­es. PTC, mean­while, has been pur­su­ing an FDA OK for ataluren, ap­proved in Eu­rope de­spite re­peat­ed fail­ures in the clin­ic. 

Not to be over­looked is Schol­ar Rock, where the ex­ec­u­tive team be­lieves they can find suc­cess by tar­get­ing la­tent rather than ac­tive myo­statin. The biotech, though, felt the heat Thurs­day morn­ing, with its shares plung­ing 12% on the news. That set­back trig­gered a flur­ry of de­fen­sive posts from an­a­lysts de­fend­ing Schol­ar Rock and bur­nish­ing their chances, with one less ri­val to wor­ry about.

Pfiz­er hasn’t quite giv­en up on its drug, leav­ing the door open to fu­ture tri­als in mus­cu­lar dis­eases. But its big re­main­ing ef­fort in DMD is in a gene ther­a­py pro­gram it has un­der­way for PF-06939926, an AAV de­liv­ered treat­ment which car­ries a short­ened ver­sion of the hu­man dy­s­trophin gene (mi­ni-dy­s­trophin).

“We are dis­ap­point­ed by these re­sults and while we are not pro­gress­ing with the stud­ies, the da­ta will con­tribute to a greater un­der­stand­ing of this dis­ease and we will eval­u­ate the to­tal da­ta set to see if there is a place for this med­i­cine in mus­cu­lar dis­eases,” said Seng Cheng, the CSO for the Pfiz­er Rare Dis­ease Re­search Unit.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

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.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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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, and could help shore up public trust in the agency and any eventual vaccine.

Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Con­tro­ver­sial hu­man chal­lenge tri­als to be­gin in Lon­don — re­port

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the biotech.

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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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Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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