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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.