A cou­ple months ahead of its PDU­FA date, Bris­tol My­ers rolls out long-term da­ta for mava­camten

It’s al­most time for the FDA to make a de­ci­sion on mava­camten, the myosin in­hibitor at the cen­ter of Bris­tol My­ers Squibb’s $13 bil­lion MyoKar­dia buy­out. With a Jan. 28 PDU­FA date loom­ing, the phar­ma gi­ant is now tak­ing the wraps off some long-term da­ta it hopes will bol­ster the drug’s case for ap­proval.

Heart pa­tients who re­ceived mava­camten in a co­hort of the long-term MA­VA-LTE study saw sig­nif­i­cant re­duc­tions in me­di­an lev­els of a hor­mone called NT-proB­NP (58% at week 24 and 67% at week 48), Bris­tol My­ers re­port­ed at this year’s Amer­i­can Heart As­so­ci­a­tion con­fer­ence. High­er than nor­mal NT-proB­NP lev­els are in­dica­tive of heart fail­ure.

Bris­tol My­ers called this a “sus­tained re­duc­tion,” adding that im­prove­ments in left ven­tric­u­lar re­lax­ation and di­as­tolic func­tion were al­so seen al­though no sig­nif­i­cant changes were ob­served in left-ven­tric­u­lar stroke vol­ume.

The phar­ma gi­ant is shoot­ing for an ap­proval in symp­to­matic ob­struc­tive hy­per­trophic car­diomy­opa­thy, or oHCM: a con­di­tion in which the mus­cu­lar wall be­tween the two bot­tom cham­bers of the heart be­comes thick­er than nor­mal, block­ing blood flow out of the heart. In ad­di­tion to be­ing at an in­creased risk of heart fail­ure and stroke, pa­tients with HCM of­ten suf­fer fa­tigue and short­ness of breath that keep them from per­form­ing dai­ly ac­tiv­i­ties.

Mava­camten was “well tol­er­at­ed” in the long-term study, Bris­tol My­ers said, though nine pa­tients paused their treat­ment be­cause left ven­tric­u­lar ejec­tion frac­tions (a mea­sure­ment of how much blood is be­ing pumped out of the heart’s left ven­tri­cle) were too low. Eight of them re­sumed treat­ment at a low­er dose af­ter re­cov­ery, while one dis­con­tin­ued the tri­al per­ma­nent­ly, the com­pa­ny said.

BMS picked up mava­camten in its MyoKar­dia buy­out last Oc­to­ber and got its NDA ac­cept­ed back in March. The drug claims to work by de­creas­ing the ex­cess bridg­ing be­tween myosin and actin, there­by coun­ter­act­ing the hy­per­tro­phy and hy­per-con­trac­til­i­ty ex­pe­ri­enced by pa­tients with oHCM.

Roland Chen

In May, Bris­tol My­ers re­leased more Phase III da­ta at the vir­tu­al Amer­i­can Col­lege of Car­di­ol­o­gy meet­ing show­ing that pa­tients on mava­camten post­ed a clin­i­cal­ly sig­nif­i­cant in­crease over place­bo in scores on the Kansas City Car­diomy­opa­thy Ques­tion­naire, a catch-all sum­ma­ry of symp­toms and qual­i­ty of life mark­ers, at 30 weeks. Mava­camten boost­ed ob­struc­tive car­diomy­opa­thy pa­tients’ scores by more than 20 points over place­bo, where a five-point in­crease was con­sid­ered “small but clin­i­cal­ly sig­nif­i­cant,” Bris­tol My­ers said in a re­lease.

“We’re very ex­cit­ed,” Bris­tol My­ers’ se­nior VP and head of car­dio­vas­cu­lar de­vel­op­ment Roland Chen said of the da­ta be­ing pre­sent­ed at AHA. “They re­in­force our con­fi­dence of mava­camten as a po­ten­tial med­i­cine for pa­tients with hy­per­trophic car­diomy­opathies.”

If ap­proved in a cou­ple months, Bris­tol My­ers says it’s ready to be­gin rolling out the drug in 2022.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

As first Omi­cron case in US crops up, re­searchers won­der: which an­ti­bod­ies, vac­cines will hold up?

As Covid-19 drug and vaccine developers race to figure out which of their products might be hampered by the new variant, the CDC on Wednesday afternoon announced the first confirmed case of the Omicron variant (B.1.1.529) in the US, found in San Francisco.

The unidentified individual was a traveler who returned from South Africa on Nov. 22, 2021, was fully vaccinated, and had mild symptoms that the CDC described as improving. All close contacts have been contacted and have tested negative, the centers said.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.