Gilead­'s selon­sert­ib fails PhI­II in less sick NASH pa­tients — to no one's sur­prise

The prospects of Gilead’s top late-stage NASH drug selon­sert­ib grew dim when it kicked off Phase III read­outs with a flop. Two months lat­er, the com­pa­ny con­ced­ed that a sec­ond, much sim­i­lar tri­al has al­so failed.

John McHutchi­son

STEL­LAR-3 set out to mea­sure how well selon­sert­ib, an oral in­hibitor of apop­to­sis sig­nal-reg­u­lat­ing ki­nase 1 (ASK1), can im­prove fi­bro­sis with­out NASH wors­en­ing. That’s the same pri­ma­ry end­point as STEL­LAR-4, ex­cept that STEL­LAR-3 re­cruit­ed pa­tients at a slight­ly ear­li­er stage of dis­ease — with F3, or bridg­ing, fi­bro­sis — com­pared to the cir­rho­sis (F4 fi­bro­sis) pa­tients en­rolled in the oth­er tri­al.

At 48 weeks, on­ly 9.3% of pa­tients treat­ed with the 18 mg dose of the drug achieved a 1-stage im­prove­ment or more in fi­bro­sis, while the 6 mg arm reg­is­tered a 12.1% suc­cess rate. Both are low­er than the 13.2% with place­bo, though the p-val­ues were 0.42 and 0.93 re­spec­tive­ly.

The fail­ure comes as lit­tle sur­prise — and thus lit­tle im­pact — to skep­tics who were quick to write off the pro­gram af­ter the ear­li­er Phase III, Baird an­a­lysts wrote in a note.

That be­ing said, Gilead could face some de­gree of rep­u­ta­tion­al harm, giv­en that this rep­re­sents the clo­sure of their sec­ond Phase 3 NASH pro­gram to fail mis­er­ably (the first of which was sim­tuzum­ab). Mov­ing for­ward, Gilead is ex­pect­ed to an­nounce his­tol­ogy da­ta from their Phase 2 tri­al of var­i­ous two drug com­bi­na­tions in NASH by the end of 2019.

Gilead re­cent­ly came up with some ear­ly da­ta to sup­port the com­bi­na­tion ap­proach, show­ing in a proof-of-con­cept study that cilofex­or and fir­so­co­stat can in­duce a sig­nif­i­cant de­cline in he­pat­ic fat — a hall­mark of the liv­er dis­ease. On top of that it’s al­so an­nounced a col­lab­o­ra­tion with di­a­betes gi­ant No­vo Nordisk, adding semaglu­tide to form a three-drug reg­i­men.

Don’t think selon­sert­ib is go­ing away, though. In line with its cock­tail strat­e­gy, Gilead has be­gun test­ing the drug in com­bi­na­tion with cilofex­or and fir­so­co­stat.

“While we had hoped for dif­fer­ent out­comes from the STEL­LAR pro­gram, we re­main fo­cused and com­mit­ted to de­vel­op­ing high­ly ef­fec­tive treat­ments for pa­tients liv­ing with ad­vanced fi­bro­sis due to NASH,” Gilead head of R&D John McHutchi­son said in a state­ment.

He added that the com­pa­ny will work with col­lab­o­ra­tors like PathAI and in­sitro to bet­ter un­der­stand the dis­ease, a yet un­met med­ical need in hot pur­suit by big and small play­ers alike.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.