Promis­ing or in­con­clu­sive? Gilead fields PhII GS-4997 da­ta, trig­ger­ing more push­back on NASH claims

Gilead post­ed a de­tailed snap­shot of Phase II ef­fi­ca­cy da­ta for GS-4997, now known as selon­sert­ib, for NASH and liv­er fi­bro­sis, trig­ger­ing a mixed re­sponse of en­thu­si­asm and some clear skep­ti­cism from the an­a­lysts watch­ing this late-stage drug, some of whom got their first crack in when Gilead out­lined the top line da­ta from this study in Oc­to­ber.

The num­bers were de­tailed for selon­sert­ib alone, in com­bi­na­tion with sim­tuzum­ab or in sim­tuzum­ab alone. And in­ves­ti­ga­tors had a mixed bag of re­sults un­der­scor­ing drug ac­tiv­i­ty, rang­ing from the 43% of pa­tients tak­ing selon­sert­ib see­ing an im­prove­ment in fi­bro­sis com­pared to the 20% in the sim­tuzum­ab arm to the 20% in the selon­sert­ib arm ex­pe­ri­enc­ing a min­i­mum 15% re­duc­tion in liv­er stiff­ness to the 32% in the com­bo group and none tak­ing sim­tuzum­ab alone.

Phase 2 Da­ta for Selon­sert­ib in Non­al­co­holic Steato­hep­ati­tis (NASH) Pre­sent­ed at The Liv­er Meet­ing® 2016.

 

Gilead $GILD ac­knowl­edged ear­li­er this month that sim­tuzum­ab has been a bust in the clin­ic, prompt­ing its R&D team to drop it com­plete­ly. It al­so has GS-9674 in ear­ly-stage stud­ies for NASH and re­cent­ly picked up an­oth­er pro­gram from Nim­bus. And NASH re­mains a key fea­ture in the pipeline as Gilead looks to over­come the hang­over from its hep C bash, where rev­enue is now de­clin­ing steadi­ly.

Bri­an Sko­r­ney, Baird

Even last month, though, an­a­lysts like Bri­an Sko­r­ney at Baird were shak­ing their head over what Gilead had to of­fer:

“The num­bers are too small, the du­ra­tion of treat­ment is too short and the da­ta is com­pli­cat­ed by the in­clu­sion of an­oth­er drug in­stead of place­bo.”

Af­ter its stun­ning suc­cess with hep C, Gilead’s R&D strat­e­gy in gen­er­al has come un­der fre­quent at­tack as skep­ti­cism grows about its abil­i­ty to over­come its grow­ing prob­lems on the rev­enue side of the busi­ness.

Ro­hit Loom­ba, the lead study au­thor and di­rec­tor of the NAFLD Re­search Cen­ter, had this to say in a state­ment:

“Af­ter on­ly 24 weeks of ther­a­py, selon­sert­ib ex­hib­it­ed promis­ing an­ti-fi­brot­ic ac­tiv­i­ty in this study, which was the first known mul­ti-cen­ter NASH clin­i­cal tri­al to use cen­tral­ly-as­sessed MRE, MRI-PDFF, in ad­di­tion to liv­er biop­sy as end­points. Based on these da­ta, selon­sert­ib rep­re­sents an im­por­tant in­ves­ti­ga­tion­al drug can­di­date for fur­ther clin­i­cal tri­als in pa­tients with NASH and sig­nif­i­cant fi­bro­sis.”

Ge­of­frey Porges, Leerink

Well, maybe, re­sponds Leerink’s Ge­of­frey Porges, who notes that this is the study that prompt­ed Gilead to go big in Phase III:

“In their most re­cent earn­ings con­fer­ence call the com­pa­ny dis­closed that the prod­uct has failed in de­vel­op­ment in oth­er in­di­ca­tions such as di­a­bet­ic nephropa­thy, and par­al­lel pro­grams in these liv­er dis­eases, in­clud­ing sim­tuzum­ab, have al­so been dis­con­tin­ued. How­ev­er, man­age­ment’s re­ac­tion to GS4997 was very pos­i­tive and sug­gest­ed im­pres­sive phase II re­sults. Our re­ac­tion to the phase II re­sults is that they do show en­cour­ag­ing signs of dis­ease ac­tiv­i­ty, but at this stage re­gard the ev­i­dence of ben­e­fit, and safe­ty and tol­er­a­bil­i­ty, as in­con­clu­sive. The ev­i­dence of ef­fect is per­sua­sive on some end­points, but un­clear on oth­ers, and the NASH field is like­ly to re­quire con­tin­ued re­search to re­fine tri­al end­points and to es­tab­lish some mean­ing­ful cor­re­la­tion be­tween those end­points and clin­i­cal ben­e­fit for pa­tients. GS4997 al­so ap­pears to have some tol­er­a­bil­i­ty li­a­bil­i­ties, which could add to the drug’s lim­i­ta­tions in both de­vel­op­ment and com­mer­cial­iza­tion.”

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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