Days ahead of Am­gen split, Cy­to­ki­net­ics reads out post-hoc da­ta sug­gest­ing heart drug works bet­ter in sick­er pa­tients — but can the CEO win over skep­tics?

While Cy­to­ki­net­ics’ heart drug tech­ni­cal­ly met its pri­ma­ry end­point back in No­vem­ber, it missed a key sec­ondary end­point — re­duc­tion in car­dio­vas­cu­lar death — which even­tu­al­ly cost the com­pa­ny two part­ner­ships. Now the team is back with da­ta sug­gest­ing the drug works bet­ter in sick­er pa­tients, and it’s plan­ning a trip to the FDA.

In a post-hoc analy­sis, which can be a very dif­fi­cult sale at the FDA, Cy­to­ki­net­ics sep­a­rat­ed pa­tients from the Phase III GALAC­TIC-HF study in­to four quar­tiles based on ejec­tion frac­tion, a mea­sure­ment of how well the left ven­tri­cle pumps blood with each heart­beat. Pa­tients in the low­er two quar­tiles — those with an EF of 22% or low­er, and be­tween 29% to 32% — saw a 15% and 17% rel­a­tive risk re­duc­tion of heart fail­ure events and car­dio­vas­cu­lar death com­bined, Cy­to­ki­net­ics re­port­ed at ACC. No dif­fer­ence was seen in the up­per two quar­tiles.

The ben­e­fi­cial ef­fect was main­ly dri­ven by a re­duc­tion in heart fail­ure events, Cy­to­ki­net­ics said. When con­sid­er­ing heart fail­ure events alone, the rel­a­tive risk re­duc­tion for the low­er two quar­tiles was 19% and 17% re­spec­tive­ly, with no dif­fer­ence seen in the up­per two quar­tiles.

Fady Ma­lik

“We en­rolled in GALAC­TIC a pa­tient pop­u­la­tion that had poor car­diac func­tion but, you know, you don’t know ahead of time, ‘Well where should we draw that line,’” ex­ec­u­tive VP of R&D Fady Ma­lik told End­points News. “If we had, say, gone with an EF of 30% or less ver­sus 35% or less, the re­sults would have looked sub­stan­tial­ly dif­fer­ent.”

Ome­cam­tiv mecar­bil works by tar­get­ing myosin, a pro­tein that con­verts chem­i­cal en­er­gy in­to me­chan­i­cal force in the heart. In Oc­to­ber, Cy­to­ki­net­ics an­nounced the drug re­duced the odds of hos­pi­tal­iza­tion or oth­er ur­gent care for heart fail­ure by 8%, a sta­tis­ti­cal­ly sig­nif­i­cant re­sult.

How­ev­er, even the sub­groups with low­er EF missed the sec­ondary end­point of a re­duc­tion in car­dio­vas­cu­lar death, which an­a­lysts have been look­ing to as a key mea­sure of suc­cess.

“In my view, with­out CV death ben­e­fit, the drug prob­a­bly won’t be a foun­da­tion­al med­i­cine and do the $4Bn in WW end-user sales that we had orig­i­nal­ly thought (con­sen­sus is ~$3.5Bn). But is it a ze­ro? Maybe not,” Mizuho’s Sal­im Syed wrote af­ter Cy­to­ki­net­ics un­veiled its topline re­sults back in Oc­to­ber.

“I think it’s pre­ma­ture for an­a­lysts, or oth­ers, to jump to con­clu­sions,” CEO Robert Blum told End­points on Fri­day.

Robert Blum

“While this is not per­haps foun­da­tion­al to the stan­dard of care for every heart fail­ure pa­tient as might have been our as­pi­ra­tion … we fore­see at Cy­to­ki­net­ics that this is a very im­por­tant un­met need for which ome­cam­tiv mecar­bil and GALAC­TIC fac­tors very im­por­tant­ly in­to what may be a so­lu­tion for these pa­tients,” he added.

Cy­to­ki­net­ics says it’s plan­ning on sub­mit­ting an NDA for the can­di­date in the sec­ond half of this year. Whether or not they’ll pur­sue an ap­proval specif­i­cal­ly for pa­tients with low­er EF is “some­thing to be de­ter­mined in con­cert with on­go­ing dis­cus­sions with FDA,” Blum said.

In just a few days, Cy­to­ki­net­ics will of­fi­cial­ly lose its long­time part­ner Am­gen, which shrugged off its 14-year al­liance and the tens of mil­lions of dol­lars it spent to de­vel­op ome­cam­tiv back in No­vem­ber. Up­on an­nounc­ing the split, Am­gen said the GALAC­TIC da­ta “did not meet the high bar we had set for the pro­gram.” A month lat­er, Les Lab­o­ra­toires Servi­er and In­sti­tut de Recherch­es In­ter­na­tionales Servi­er said it was al­so pulling out of a sub­li­cense agree­ment for ome­cam­tiv that it struck with Am­gen back in 2016.

At the time, Blum in­sist­ed on look­ing at the bright side, an­nounc­ing he was “pleased to pro­ceed in­to 2021 with clar­i­ty.”

When asked about the pos­si­bil­i­ty of fu­ture col­lab­o­ra­tions, Blum said the com­pa­ny is in talks with “quite a num­ber of com­pa­nies” to com­mer­cial­ize ome­cam­tiv out­side the US. Cy­to­ki­net­ics plans on mar­ket­ing the drug on its own with­in the US, both Blum and Ma­lik said.

“You’ve got here a group of pa­tients — not a small group at all, on the or­der of one to two mil­lion pa­tients prob­a­bly in the Unit­ed States — who are se­vere­ly ill, and are maxed out on stan­dard of care. And yet with these analy­ses, we see they rep­re­sent a pop­u­la­tion that needs a new ther­a­py,” Blum said.

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

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What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

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Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

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David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

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Reshma Kewalramani, Vertex CEO (BIO via YouTube)

UP­DAT­ED: Ver­tex strikes out on its lat­est big shot at a rare ge­net­ic dis­ease. But they're go­ing to keep on swing­ing

It’s been several months since Vertex culled one of its small molecules for alpha-1 antitrypsin deficiency (AATD), taking a big hit after evidence of liver damage surfaced in a key Phase II trial. Now we learned that the company has whiffed on its second shot, and there’s nothing left in the clinic to treat the rare genetic disease — but that won’t stop it from trying.

Despite avoiding the safety issues that plagued the last candidate, Vertex $VRTX is taking the axe to VX-864 after Phase II results revealed the magnitude of the drug’s response is “unlikely to translate into substantial clinical benefit.” As a result of the news, the company’s stock fell 12.5% after hours.

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FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

Paul Hudson, Sanofi CEO (Eric Piermont/AFP via Getty Images)

Months af­ter FDA re­jec­tion, Sanofi touts piv­otal win for rare dis­ease drug su­tim­limab as it preps to re­file

One of the pillar drugs of Sanofi’s $11.6 billion pickup of Bioverativ hit a big setback late last year when the FDA sent its application for approval back. Now, as Sanofi gears up to resubmit the drug for review, the drugmaker is touting pivotal data it hopes will help take it over the finish line.

Sanofi’s sutimlimab nailed all three of its primary endpoints in its Phase III CADENZA study for patients with cold agglutinin disease, a rare disorder that can cause severe anemia, without a recent history of blood transfusion, the French drugmaker said Friday. The topline results will be presented at this weekend’s virtual EHA meeting.

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Ver­tex and CRISPR Ther­a­peu­tics un­veil more pos­i­tive gene ther­a­py da­ta, but busul­fan again casts a shad­ow over the field

Less than 12 hours after revealing a flop on its second shot for alpha-1 antitrypsin deficiency, Vertex plowed ahead with another data drop from its partnership with CRISPR Therapeutics. And though the topline proved positive, concerns over conditioning agents continue to linger over the collaboration, as well as the entire gene therapy space.

Presenting data from two trials at the European Hematology Association annual meeting, the pair announced that follow-up data of at least three months for 22 patients with genetic blood disorders indicated a “consistent and sustained” response to the experimental drug CTX001. All 15 patients with transfusion-dependent beta thalassemia did not need further blood transfusions and all seven with severe sickle cell disease were pain free, the biotechs announced.

Janet Woodcock, acting FDA commissioner, at Thursday's Senate Appropriations hearing (Bill Clark/CQ Roll Call via AP Images)

Sen­a­tors lam­bast new Alzheimer’s drug’s price but give Janet Wood­cock a free pass on the ap­proval de­ci­sion

Senate Finance Democrats took aim at Biogen’s pricey new Alzheimer’s drug on Thursday, but members on both sides of the aisle at a separate appropriations hearing didn’t question acting FDA commissioner Janet Woodcock on the approval.

“I was appalled that Biogen priced their Alzheimer’s drug approved by the FDA at $56,000 per year — I’m not going to debate whether this is effective or not, but it’s double the household median income for Michiganders over the age of 65,” Sen. Debbie Stabenow (D-MI) said at the finance hearing.