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.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

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FDA to Sarep­ta: Your wide­ly an­tic­i­pat­ed fol­lowup to Ex­ondys 51 is not get­ting an ac­cel­er­at­ed OK for Duchenne MD

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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UP­DAT­ED: No­var­tis spin­off Nabri­va fi­nal­ly scores its first an­tibi­ot­ic ap­proval

In May, Nabriva Therapeutics suffered a setback after the FDA rejected its antibiotic for complicated urinary tract infections — the Novartis spinoff has now had some better luck with the US agency, which on Monday approved its other drug for community-acquired bacterial pneumonia.

The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.

Saqib Islam. CheckRare via YouTube

Spring­Works seeks $115M to push Pfiz­er drugs across fin­ish line while Sat­suma sells mi­graine play in $86M IPO

SpringWorks and Satsuma — both biotech spinouts that have closed B rounds in April — are loading up with IPO cash to boost their respective late-stage plans.
SpringWorks

Bain-backed SpringWorks is the better-known company of the two, and it’s gunning for a larger windfall of $115 million to add to $228 million from previous financings. In the process, the Stamford, CT-based team is also drawing the curtains on the partnerships it has in mind for the pair of assets it had initially licensed from Pfizer.

Mi­nor­i­ty racial groups con­tin­ue to be dis­mal­ly rep­re­sent­ed in can­cer tri­als — study

Data reveal that different racial and ethnic groups — by nature and/or nurture — can respond differently in terms of pharmacokinetics, efficacy, or safety to therapeutics, but this disparity is not necessarily accounted for in clinical trials. A fresh analysis of the last decade of US cancer drug approvals suggests the trend continues, cementing previous research that suggests oncology trials are woefully under-representative of the racial makeup of the real world.

Van­da shares slide af­ter FDA spurns their big end­point and re­jects a pitch on jet lag re­lief

Back in the spring of last year, Vanda Pharmaceuticals $VNDA served up a hot stew of mixed data for a slate of endpoints related to what they called clear evidence that their melatonin sleep drug Hetlioz (tasimelteon) could help millions of travelers suffering from jet lag.

Never mind that they couldn’t get a planned 90 people in the study, settling for 25 instead; Vanda CEO Mihael H. Polymeropoulos said they were building on a body of data to prove it would help jet-lagged patients looking for added sleep benefits. And that, they added, would be worth a major upgrade from the agency as they sought to tackle a big market.