Cy­to­ki­net­ics ax­es lead drug af­ter it im­plodes in a PhI­II mus­cle tri­al for ALS, shares crater

Cy­to­ki­net­ics $CYTK lead mus­cle drug has crashed in a Phase III study for ALS.

The biotech re­port­ed this morn­ing that tirasem­tiv, de­signed to amp up the mus­cles of sick pa­tients, failed to hit the pri­ma­ry end­point on what’s called slow vi­tal ca­pac­i­ty, which mea­sures how much air can be ex­haled. And now the ther­a­py is be­ing shelved as the biotech’s stock craters, plung­ing more than 30% Tues­day morn­ing.

Robert Blum

The de­cline in SVC was slow­er in the drug arms com­pared to a place­bo, but it nev­er achieved sta­tis­ti­cal sig­nif­i­cance. The mid- and high-dose arms had the best re­spons­es, but it wasn’t enough. And now the South San Fran­cis­co-based biotech plans to shift fo­cus to a next-gen drug in the pipeline, where it feels it has a bet­ter shot at suc­cess, and kill the tirasem­tiv pro­gram.

That’s al­so bad news for Astel­las, which com­mit­ted $95 mil­lion in cash to Cy­to­ki­net­ics in or­der to get an op­tion on the drug as well as the ear­li­er-stage ther­a­py Cy­to­ki­net­ics will now turn to. Astel­las al­so in­clud­ed up to $100 mil­lion in mile­stones for the work.

While dis­ap­point­ing for in­vestors, it can’t be a big sur­prise to re­searchers in the field. Three years ago Cy­to­ki­net­ics re­port­ed that tirasem­tiv — which is de­signed to in­crease mus­cle sen­si­tiv­i­ty to cal­ci­um –flunked the pri­ma­ry and a range of sec­on­daries for ALS, scor­ing on­ly on SVC. Failed mid-stage drugs face tough odds when they are pushed in­to late-stage test­ing, as Cy­to­ki­net­ics knows all too well this morn­ing.

ALS re­mains one of the tough­est tar­gets in drug R&D, de­feat­ing mul­ti­ple at­tempts at ad­dress­ing a dis­ease that in­volves mo­tor neu­rons and the steady and re­morse­less de­cline of a pa­tient’s mus­cle ac­tiv­i­ty, lead­ing to death. Rilu­zole was the on­ly drug ap­proved for ALS in the US, ar­riv­ing in 1995, and re­mained in a class by it­self un­til Mit­subishi Tan­abe’s Rad­i­ca­va was added ear­li­er this year. Nei­ther come close to stop­ping the dis­ease.

Cy­to­ki­net­ics CEO Robert Blum not­ed:

We have de­cid­ed to sus­pend the de­vel­op­ment of tirasem­tiv. While we be­lieve that VI­TAL­I­TY-ALS demon­strat­ed phar­ma­co­log­ic ac­tiv­i­ty for the mech­a­nism of ac­tion, we al­so be­lieve that lim­i­ta­tions of tirasem­tiv may be ad­dressed with our next-gen­er­a­tion fast skele­tal mus­cle ac­ti­va­tor, CK-2127107.  Based on pre­vi­ous Phase 1 clin­i­cal stud­ies, we be­lieve CK-2127107 will be bet­ter tol­er­at­ed and po­ten­tial­ly more ef­fec­tive than tirasem­tiv in pa­tients with ALS and look for­ward to Phase 2 tri­al re­sults in 2018.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

Dutch biotech starts liq­ui­da­tion af­ter end­ing PhI­II in GVHD

A 13-year-old Dutch biotech is going through a liquidation process after an unexpected end to its Phase III trial testing whether its combination of two monoclonal antibodies was superior to Incyte’s Jakafi.

Xenikos had hoped to prove its investigational therapy, named T-Guard, was better than Jakafi at garnering a complete response in patients experiencing life-threatening complications in which new cells from a hematopoietic stem cell transplant begin to fight the body. Jakafi was approved for the indication, steroid-refractory acute graft-versus-host disease, in May 2019.

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Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

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