Am­gen sev­ers 14-year Cy­to­ki­net­ics part­ner­ship, bail­ing on ome­cam­tiv af­ter mixed PhI­II re­sults

Am­gen is shrug­ging off a 14-year de­vel­op­ment al­liance and the tens of mil­lions of dol­lars spent to de­vel­op a new heart drug at Cy­to­ki­net­ics af­ter a Phase III tri­al turned up weak da­ta — leav­ing Cy­to­ki­net­ics to sol­dier on alone.

Ome­cam­tiv mecar­bil tech­ni­cal­ly worked, meet­ing the pri­ma­ry com­pos­ite end­point in the Phase III GALAC­TIC-HF study. But it missed a key sec­ondary end­point, which an­a­lysts had been fol­low­ing as a key mark­er for suc­cess — re­duc­tion of car­dio­vas­cu­lar (CV) death. While Cy­to­ki­net­ics cel­e­brat­ed the re­sults, its stock tanked 43% up­on the news, and an­a­lysts warned of an un­cer­tain path ahead. Now, Am­gen wants out.

“Car­dio­vas­cu­lar dis­ease is one of the most sig­nif­i­cant pub­lic health is­sues in the world which means pa­tients need more in­no­va­tion, not less,” Am­gen said in a state­ment on Mon­day. “…Un­for­tu­nate­ly, the re­sults of GALAC­TIC-HF did not meet the high bar we had set for the pro­gram.”

Robert Blum

In an in­ter­view with End­points News ear­li­er this month, Cy­to­ki­net­ics CEO Robert Blum said whether they’ll ap­proach reg­u­la­tors was still up for dis­cus­sion. But de­spite the loss of their long­time part­ner, Blum said in an in­vestor call on Mon­day that he doesn’t “fore­see a sce­nario in which we do not en­gage reg­u­la­to­ry au­thor­i­ties, and seek feed­back around a po­ten­tial reg­is­tra­tion path for­ward.”

In ad­di­tion to ome­cam­tiv, Am­gen is re­turn­ing the rights to AMG 594, a Phase I can­di­date in de­vel­op­ment for HFrEF and oth­er types of heart fail­ure. On the in­vestor call, Blum spun the set­back as an op­por­tu­ni­ty to “re­claim” the can­di­dates and go the path alone.

SVB Leerink an­a­lysts saw this com­ing. “We agree with Am­gen that ome­cam­tiv is un­like­ly to be a com­pet­i­tive drug in heart fail­ure with re­duced ejec­tion frac­tion (HFrEF), as the large Phase 3 study failed to achieve the high bar that in­vestors/com­pa­ny had ex­pect­ed (ex­pect­ing >20% CV risk re­duc­tion and mor­tal­i­ty ben­e­fit),” Ge­of­frey Porges, Ke Yuan and Charles Song wrote in a note to in­vestors on Mon­day.

“We don’t ex­pect Am­gen’s stock to move sig­nif­i­cant­ly on this news as most in­vestors had al­ready dis­count­ed the po­ten­tial of this pro­gram af­ter the topline re­sult was an­nounced in ear­ly Oc­to­ber,” they added.

John Teer­link

Cy­to­ki­net­ics’ stock was up 0.53% on Mon­day, hov­er­ing around $16 a share.

Ome­cam­tiv mecar­bil works by tar­get­ing myosin, a pro­tein that con­verts chem­i­cal en­er­gy in­to me­chan­i­cal force in the heart. Since 2005, it’s been through 11 Phase I stud­ies with over 300 pa­tients and 7 Phase II stud­ies with over 1,400 pa­tients.

In the 8,250-per­son GALAC­TIC-HF study, it re­duced the odds of hos­pi­tal­iza­tion or oth­er ur­gent care for heart fail­ure by 8%. The risk of first heart fail­ure event was re­duced by 7% in the treat­ment arm, but it “did not in­di­vid­u­al­ly reach sta­tis­ti­cal sig­nif­i­cance with a nom­i­nal p val­ue of 0.06,” Uni­ver­si­ty of Cal­i­for­nia San Fran­cis­co pro­fes­sor and GALAC­TIC-HF ex­ec­u­tive com­mit­tee chair John Teer­link said in a call with in­vestors a cou­ple of weeks ago. Over­all change in con­di­tion — mea­sured us­ing the Kansas City Car­diomy­opa­thy Ques­tion­naire — al­so failed to achieve sta­tis­ti­cal sig­nif­i­cance, Teer­link said.

At AHA, Blum tout­ed the re­sults from cer­tain sub­groups of pa­tients, in­clud­ing those with low­er ejec­tion frac­tion, which he said the drug had a “dou­bling ef­fect on.” Ex­ec­u­tive VP of R&D Fady Ma­lik said this month that there were some groups of more se­vere” pa­tients in which the drug had a greater ef­fect.

Fady Ma­lik

But oth­ers aren’t see­ing much of a sil­ver lin­ing. “While the CV ben­e­fits seem to be re­al and bet­ter, it re­mains un­clear if the ex­ist­ing dataset is suf­fi­cient to sup­port a reg­u­la­to­ry fil­ing based on this pre-spec­i­fied sub­group analy­sis,” the SVB Leerink an­a­lysts wrote af­ter the AHA pre­sen­ta­tion. Mizuho’s Sal­im Syed wrote that Cy­to­ki­net­ics will need to “ex­e­cute a bit more on ome­cam­tiv and show in­vestors there is a path.”

Am­gen paid Cy­to­ki­net­ics $42 mil­lion in up­front and tech­nol­o­gy ac­cess fees to de­vel­op and com­mer­cial­ize the drug back in 2007. It al­so pur­chased 3.4 mil­lion shares of the biotech’s com­mon stock at $9.47 apiece, to­tal­ing about $33 mil­lion.

Am­gen grant­ed a sub­li­cense to Les Lab­o­ra­toires Servi­er and In­sti­tut de Recherch­es In­ter­na­tionales Servi­er to com­mer­cial­ize ome­cam­tiv in Eu­rope and the Com­mon­wealth of In­de­pen­dent States, in­clud­ing Rus­sia, back in 2016. The sub­li­censed rights are still in ef­fect, now un­der Cy­to­ki­net­ics.

The re­cent news adds to a tu­mul­tuous cou­ple of years for Cy­to­ki­net­ics, which has strug­gled to meet key end­points in its ALS tri­als. Its lead mus­cle drug crashed and burned in a Phase III ALS tri­al, and its relde­sem­tiv flopped in a Phase II study last year.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.