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.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

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While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA.