Gen­fit's NASH drug fails a close­ly-watched PhI­II show­down, adding one more set­back to a plagued field

Gen­fit’s bid to make R&D his­to­ry with a sto­ry­book turn­around came to a crash­ing halt on Mon­day as the French biotech ac­knowl­edged that its Phase III study of elafi­bra­nor failed to dis­tin­guish it­self from place­bo in treat­ing NASH.

Pas­cal Pri­gent

The biotech had tried to prove that the drug would re­solve NASH with­out fi­bro­sis in a pop­u­la­tion of more than 1,000 pa­tients. But the da­ta came up with a 19.2% re­sponse rate for the drug arm com­pared to a 14.7% rate for the place­bo.

Gen­fit CEO Pas­cal Pri­gent put down the “dis­ap­point­ing” re­sult to a high place­bo re­sponse, though the drug arm didn’t ap­pear to score all that high in the study.

The CEO not­ed:

We plan to share these de­tailed find­ings with the reg­u­la­to­ry au­thor­i­ties in the com­ing months and with their guid­ance, de­ter­mine a fi­nal de­ci­sion re­gard­ing the con­tin­u­a­tion of the RE­SOLVE-IT tri­al. In par­al­lel, we con­tin­ue as planned with our NIS4TM and Phase 3 PBC (pri­ma­ry bil­iary cholan­gi­tis) pro­grams, which are in­de­pen­dent of our NASH pro­gram with elafi­bra­nor. We will pro­vide up­dat­ed guid­ance on our glob­al cor­po­rate strat­e­gy lat­er in the year, once we have more clar­i­ty on the reg­u­la­to­ry im­pli­ca­tions of the RE­SOLVE-IT in­ter­im read­out, as well as more vis­i­bil­i­ty on the evo­lu­tion of the im­pact of the world­wide pan­dem­ic on our on­go­ing stud­ies.

Last year saw mul­ti­ple set­backs in NASH, with In­ter­cept as the sole ex­cep­tion to the rule. That left some an­a­lysts cau­tious­ly en­cour­ag­ing in­vestors to look at Gen­fit, even though the odds were daunt­ing.

SVB Leerink’s Pasha Sar­raf had been on the pro-Gen­fit side­lines, call­ing this study “the most sig­nif­i­cant and volatile up­com­ing cat­a­lyst” they cov­er. “The risk/re­ward is not for the faint of heart.”

There were al­so plen­ty of skep­tics along the way, par­tic­u­lar­ly af­ter Gen­fit not­ed a Phase II NASH fail­ure for GOLD­EN-505 in 2015, then tried to ex­plain it all away as a fail­ure of the tri­al de­sign.

The fail­ure leaves In­ter­cept $ICPT as the sole win­ner in this field so far, with Ocali­va un­der re­view for a la­bel ex­pan­sion on NASH.

Iron­i­cal­ly, on the same day that Gen­fit raised fresh ques­tions about the PPAR class, a ri­val in the class — CymaBay — popped up look­ing for a sec­ond chance. Michael Yee at Jef­feries not­ed:

CBAY which has a Ph II PPAR-delta fo­cused mol­e­cule but pre­vi­ous­ly halt­ed the pro­gram due to liv­er-in­jury sig­nals & FDA hold, an­nounced on the same day that an in­de­pen­dent ex­pert pan­el unan­i­mous­ly con­clud­ed there is no ev­i­dence of drug-in­duced liv­er in­jury, & they will re-en­gage with the FDA to see if they can lift the hold. It’s un­clear to us what will hap­pen but over­all we would re­main cau­tious on the big­ger pic­ture view that a PPAR which was halt­ed in Ph II will com­plete­ly re­move the safe­ty ques­tions un­til a full Ph III would be com­plet­ed.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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The fu­ture of mR­NA, J&J's vac­cine ad­comm, Mer­ck­'s $1.85B au­toim­mune bet and more

Welcome to the third installment of Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

If this report was helpful in recapping it all for you, please do share it with your colleagues.

Get ready for FDA’s third Covid-19 vaccine

On the heels of a ringing endorsement from FDA reviewers earlier in the week, J&J‘s single-dose vaccine — which proved 66% effective at preventing symptomatic Covid-19, and 85% effective at stopping severe disease 28 days after administration — the advisory committee convened by the agency voted unanimously to recommend its emergency use authorization. It was “a relatively easy call,” according to one of the committee members — although that doesn’t mean they didn’t have questions. Jason Mast has the highlights from the discussion, including new information from the company, on this live blog.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Roche and Genen­tech re­searchers plot $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Roche and Genentech have committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Researchers from both Roche and its big South San Francisco hub — mixing teams from gRED and pRED this time — will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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