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.

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.