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.

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.

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.

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.