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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,400+ biopharma pros reading Endpoints daily — and it's free.

Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

News brief­ing: Tiny Vac­cinex's drug flops in PhII Hunt­ing­ton's tri­al, stock craters; Siol­ta nabs $30M Se­ries B to de­vel­op mi­cro­bio­me drug

Siolta Therapeutics, a microbiome company targeting allergic diseases, raked in a $30 million Series B to develop its lead candidate, STMC-103H. The drug, which has been FDA fast-tracked, is headed for proof-of-concept trials, according to the company. Its various indications include allergic asthma, food allergies, atopic dermatitis, allergic rhinitis, and allergy prevention.

The news comes just after the California-based biotech added a prominent biopharma veteran as an advisor: 20-year Gilead CEO John Martin. The biotech also gained Richard Shames as CMO, who came by way of Protagonist Therapeutics.

Embattled CDC director Robert Redfield (AP Images)

Covid-19 roundup: CDC ad­vi­so­ry com­mit­tee de­lays pri­or­i­ty dis­tri­b­u­tion vote; EU re­port­ed­ly in­dem­ni­fy­ing vac­cine mak­ers

A federal committee that advises the CDC was expected to hold a vote Tuesday on a plan regarding the distribution for initial doses of approved Covid-19 vaccines. But that vote has been scrapped.

The Advisory Committee on Immunization Practices, or ACIP, won’t be voting until the committee members learn more about which vaccines become available first, the Wall Street Journal reported. The vote could potentially wait until a specific vaccine is authorized before recommending how to dole out the first doses.

Zai Lab hauls in $761M from Hong Kong IPO to push Ze­ju­la, more bud­ding can­di­dates in Chi­na — re­port

Zai Lab is set to net more than $761 million from its secondary listing in Hong Kong after pricing the IPO at $72.51 (HKD$562) — just a hair below its Nasdaq closing price on Monday, Bloomberg and Nikkei Asian Review reported.

A pioneer in bringing Western drugs to China, co-founder and CEO Samantha Du has more than tripled Zai Lab’s market cap in the three years it’s been public in the US. The HKEX listing is designed to fund R&D and commercialization for the current portfolio while fueling new in-licensing pacts, the biotech wrote in a filing.