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.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

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Chris Anzalone, Arrowhead CEO

Take­da, Ar­row­head spot­light da­ta from small tri­al show­ing RNAi works in a rare liv­er con­di­tion

Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

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Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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A Mer­ck part­ner is sucked in­to the fi­nan­cial quag­mire as key lender calls in a note

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

Biden and G7 na­tions of­fer funds for vac­cine and med­ical prod­uct man­u­fac­tur­ing project in Sene­gal

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.

Fed­er­al judge de­nies Bris­tol My­er­s' at­tempt to avoid Cel­gene share­hold­er law­suit

Some Celgene shareholders aren’t happy with how Bristol Myers Squibb’s takeover went down.

On Friday, a New York federal judge ruled that they have a case against the pharma giant, denying a request to dismiss allegations that it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR).

When Bristol Myers put down $74 billion to scoop up Celgene back in 2019, liso-cel — the CAR-T lymphoma treatment now marketed as Breyanzi — was supposedly one of the centerpieces of the deal. After going back and forth on negotiations for about six months, BMS put $6.4 billion into a CVR agreement that required an FDA approval for Zeposia, Breyanzi and Abecma, each by an established date.

David Hung, Nuvation Bio president and CEO (Nuvation Bio)

FDA places par­tial clin­i­cal hold on David Hung biotech af­ter cer­tain can­cer pa­tients ex­pe­ri­ence eye in­flam­ma­tion

Two and a half years after setting out on another foray into oncology R&D, a biotech headed by David Hung — of Medivation fame — has run into its first setback.

San Francisco-based Nuvation Bio announced early Monday the FDA placed a partial clinical hold on a Phase I dose-escalation study of NUV-422, its CDK inhibitor program for certain types of solid tumors. The trial began enrolling patients in December 2020, and, according to Nuvation, researchers were in the middle of exploring dose escalation and defining the maximum dose tolerable in patients.