FDA de­lays its de­ci­sion on Bris­tol My­er­s' $13B heart drug an­oth­er three months

Last week, Bris­tol My­ers Squibb marched out long-term da­ta for its heart drug mava­camten ahead of what ex­ecs had hoped would be a pos­i­tive FDA de­ci­sion in Jan­u­ary. But reg­u­la­tors are say­ing they need a bit more time to think.

The FDA has ex­tend­ed mava­camten’s PDU­FA date three months, from Jan. 28 to April 28, Bris­tol My­ers an­nounced on Fri­day. The news came just a few days af­ter in­de­pen­dent drug pric­ing watch­dog ICER raised con­cerns about the can­di­date’s long-term safe­ty in its fi­nal ev­i­dence re­port.

Mava­camten, a myosin in­hibitor, was the cen­ter­piece of BMS’ $13 bil­lion MyoKar­dia buy­out last Oc­to­ber. The phar­ma gi­ant’s shoot­ing for an ini­tial in­di­ca­tion 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 an ab­stract at the Amer­i­can Heart As­so­ci­a­tion con­fer­ence, BMS said HCM pa­tients who took mava­camten saw a “sus­tained re­duc­tion” of a hor­mone called NT-proB­NP through Week 48. High­er than nor­mal NT-proB­NP lev­els are in­dica­tive of heart fail­ure.

How­ev­er, the com­pa­ny re­port­ed that nine pa­tients paused treat­ment be­cause their 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 the pa­tients re­sumed treat­ment at a low­er dose af­ter re­cov­ery, while one dis­con­tin­ued the tri­al per­ma­nent­ly, the com­pa­ny said.

BMS says the FDA re­quest­ed more time to “re­view in­for­ma­tion per­tain­ing to up­dates to the pro­posed Risk Eval­u­a­tion Mit­i­ga­tion Strat­e­gy (REMS),” and that no ad­di­tion­al da­ta or stud­ies have been re­quest­ed.

Mizuho’s Sal­im Syed spec­u­lat­ed that the de­lay seems to be mol­e­cule-spe­cif­ic, and not class-spe­cif­ic, not­ing that no pa­tients saw EF be­low 40% in Cy­to­ki­net­ics’ Phase II study for its myosin in­hibitor afi­camten (al­so known as CK-274). In that drug’s dose-range find­ing tri­al, one pa­tient ex­pe­ri­enced a tran­sient de­crease in LVEF that re­quired dose ad­just­ment, but not dose in­ter­rup­tion, Cy­to­ki­net­ics said.

Samit Hi­rawat

Ejec­tion frac­tion is con­sid­ered nor­mal if it’s in the range of 50% to 70%. Of the sev­en mava­camten pa­tients who ex­pe­ri­enced EF be­low 50% in the Phase III EX­PLOR­ER-HCM tri­al, one pa­tient had an EF be­low 40%.

“This is the pri­ma­ry rea­son we be­lieve the REMS is mol­e­cule-spe­cif­ic and should be treat­ed as such ⁠— these are clear­ly two dif­fer­ent safe­ty datasets,” Syed said in a note to in­vestors on Fri­day. “The PDU­FA de­lay should al­so be help­ful to­ward en­rolling US pa­tients in CK-274’s Ph3 SE­QUOIA-HCM study, where ‘start-up ac­tiv­i­ties’ are ‘un­der­way.’

While ICER not­ed that mava­camten may de­liv­er im­por­tant ben­e­fits for HCM pa­tients with few­er side ef­fects than oth­er drugs, the or­ga­ni­za­tion sug­gest­ed more da­ta are nec­es­sary to as­sess long-term safe­ty:

While mava­camten im­proved phys­i­o­log­ic pa­ra­me­ters and symp­toms in the EX­PLOR­ER tri­al, the avail­able da­ta are most­ly short term, and symp­to­matic HOCM, once it ap­pears, can last a life­time. Clin­i­cal ex­perts dif­fered on whether the re­duc­tions in ejec­tion frac­tion with mava­camten re­flect­ed ben­e­fi­cial im­prove­ments in car­diac func­tion, in­clud­ing healthy re­mod­el­ing, or wor­ri­some changes that could be as­so­ci­at­ed with clin­i­cal harm with longer ob­ser­va­tion times.

Bris­tol My­ers re­mains con­fi­dent in the drug, with CMO Samit Hi­rawat stat­ing: “We look for­ward to con­tin­u­ing to work close­ly with the FDA to bring this im­por­tant med­i­cine to pa­tients.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.

ProFound Therapeutics founding team

Flag­ship's lat­est biotech could turn some of the thou­sands of new pro­teins it dis­cov­ered in­to ther­a­pies — and it has $75M to start

Flagship Pioneering, the incubator of Moderna and dozens of other biotechs, says it has landed upon tens of thousands of previously undiscovered human proteins. The VC shop wants to potentially turn them into therapeutics.

Like other drug developers that have turned proteins into therapeutics (think insulin for diabetes), Flagship’s latest creation, ProFound Therapeutics, wants to tap into this new trove of proteins as part of its mission to treat indications ranging from rare diseases to cancer to immunological diseases.

Richard Silverman, Akava Therapeutics founder and Northwestern professor

This time around, Lyri­ca's in­ven­tor is de­vel­op­ing his North­west­ern dis­cov­er­ies at his own biotech

Richard Silverman was left in the dark for the last five years of clinical development of the drug he discovered. The Northwestern University professor found out about the first approval of Lyrica, in the last few days of 2004, like most other people: in the newspaper.

What became one of Pfizer’s top-selling meds, at $5 billion in 2017 global sales before losing patent protection in 2019, started slipping out of his hands when Northwestern licensed it out to Parke-Davis, one of two biotechs that showed interest in developing the drug in the pre-email days, when the university’s two-person tech transfer team had to ship out letters to garner industry appetite.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,700+ biopharma pros reading Endpoints daily — and it's free.

Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,700+ biopharma pros reading Endpoints daily — and it's free.

David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,700+ biopharma pros reading Endpoints daily — and it's free.

Up­dat­ed: US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

Almirall is tapping artificial intelligence on behalf of its sales force for insights and efficiencies. (via Shutterstock)

Almi­rall rolls out sales rep ar­ti­fi­cial in­tel­li­gence sys­tem, cut­ting pre-call prep and 'wind­shield time'

Dermatology specialty pharma Almirall is making its sales reps smarter. Not with extra training or educational courses, but instead with artificial intelligence tools.

It began a soft launch of a sales rep AI and machine learning platform it calls Polaris last August in one of its 7 US coverage regions. The platform from Aktana gathers information from across Almirall internal sources and external ones – such as claims and prescribing data – to generate insights for reps. Now, instead of spending hours prepping for a sales call, Polaris can generate details about a physician’s preferences, past behaviors and prescription habits for reps in minutes, said Almirall head of commercial operations Vincent Cerio.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,700+ biopharma pros reading Endpoints daily — and it's free.