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.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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José Baselga, AstraZeneca cancer chief (Brent N. Clarke/FilmMagic via Getty Images)

As­traZeneca's Calquence nabs an­oth­er win against Im­bru­vi­ca, but Eli Lil­ly is on its heels

Three years after first launching Calquence as a second generation BTK inhibitor, AstraZeneca continues to tout new data to compete with J&J and AbbVie’s first generation blockbuster Imbruvica.

The British pharma announced on Monday that Calquence passed a head-to-head Phase III study against Imbruvica in chronic lymphocytic leukemia, proving non-inferior — i.e. just as good — as the older drug. Although AstraZeneca did not break down any of the numbers, they said the drug proved superior on safety, triggering fewer cases of atrial fibrillation, an irregular heartbeat that can lead to stroke or heart failure.

Ron Cooper, Albireo CEO

Al­bireo just ad­vanced down to the 10-yard line at the FDA. And Ron Coop­er’s team is get­ting prepped for the next big play

When Albireo Pharma’s board $ALBO moved to bring in Ron Cooper as the CEO more than 5 years ago, the development-stage company went with an experienced commercial player who had a big-time position on his resume after running Bristol Myers’ commercial ops in Europe.

Now, after successfully navigating a pivotal study, putting them in a foot race with a rival toward an FDA OK, Cooper is getting a boost from regulators on the last drive back to an arena he understands completely.

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Roche amps up its bis­pe­cif­ic at­tack on Eylea with more PhI­II da­ta — but just how threat­en­ing is it?

Roche has another stack of data to back up its longer-acting challenger to Eylea — although it’s still far from certain just how much they can threaten Regeneron’s dominance.

The latest Phase III results come from two trials that enrolled 1,329 patients with neovascular age-related macular degeneration. With 45% of people in both studies getting faricimab 16 weeks apart during the first year, the bispecific still induced the same level of gains in visual acuity as Eylea every 8 weeks did, Roche’s Genentech reported.

Can strug­gling Iterum turn the cor­ner to an an­tibi­ot­ic suc­cess sto­ry? They will know in six months

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

Bahija Jallal, Immunocore

Buried in Im­muno­core's IPO fil­ings? A kick­back scheme from a now for­mer em­ploy­ee

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.