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.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

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Anap­tys­Bio's etokimab pro­vides more dis­ap­point­ing re­sults, rais­ing ques­tions about com­pound's fu­ture

The lead program for AnaptysBio’s in-house pipeline has hit another setback.

Etokimab, an IL-33 inhibitor, did not achieve statistically significant improvement in a Phase II trial for patients suffering from chronic rhinosinusitis with nasal polyps. Researchers measured the individuals’ bilateral nasal polyps score and sino-nasal outcome test, finding that neither improved upon a placebo after both four- and eight-week time markers, though they did demonstrate improvement over baseline levels of the examinations.

Brian Stuglik, Verastem CEO

The du­velis­ib hot pota­to is tossed to a new own­er as Ve­rastem looks to re­or­ga­nize around the pipeline

When Infinity put up duvelisib for a no-money-down instant deal, the biotech was looking for a quick exit from a clinical disaster. AbbVie had walked away from their alliance after looking at how the data stacked up in a crowded field.

And while it was approvable, it wasn’t looking pretty to anyone who thought in commercial terms.

One Big Pharma’s trash, though, was seen as a biotech treasure as a deeply troubled Verastem stepped up to grab the PI3K-delta/gamma — promising to run it across the goal lines at the FDA. And they did just that, only with little to show for it.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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Vi­da Ven­tures co-leads Dyne's $115M megaround for next-gen oli­go ther­a­pies aimed square­ly at mus­cles

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that it’s got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.