Rid­ing a PhII suc­cess, a small French biotech lands a rare 'break­through' sta­tus in NASH

For all the hype NASH drugs have re­ceived, the FDA has not been quick to roll out the red car­pet for the most talked-about com­pounds. The agency gave break­through des­ig­na­tion to In­ter­cept’s obeti­cholic acid in 2015 but, since then, have de­clined to of­fer that seal to oth­er late-stage drugs, in­clud­ing those from Gilead or Gen­fit.

On Mon­day af­ter­noon, though, the French biotech In­ven­ti­va an­nounced that they had won break­through sta­tus, be­com­ing — by their count — the first com­pa­ny to re­ceive the des­ig­na­tion for a NASH drug since In­ter­cept did 5 years ago. It was enough to send the com­pa­ny’s stock up 6%, from $13.65 to $14.50 pre-mar­ket.

The des­ig­na­tion comes in the wake of a se­ries of set­backs across NASH pipelines, in­clud­ing the FDA’s de­ci­sion ear­li­er this year to re­ject In­ter­cept’s obeti­cholic acid on the ap­par­ent grounds that it did not show strong enough ev­i­dence for ef­fi­ca­cy. The sur­prise CRL capped a year and a half of dis­ap­point­ments that shift­ed in­dus­try fo­cus to a host of new­er, small­er biotechs and their ear­li­er-stage com­pounds.

In June, In­ven­ti­va an­nounced that its lead drug, lan­i­fi­bra­nor, was suc­cess­ful in a Phase II tri­al. Across near­ly 250 vol­un­teers, 49% of those who re­ceived the high dose of the drug saw their liv­er cell in­flam­ma­tion and bal­loon­ing de­cline by at least two points on a stan­dard scale and didn’t see their fi­bro­sis wors­en, com­pared to 27% on place­bo. The tri­al al­so hit sec­ondary end­points at low and high dose for NASH res­o­lu­tion and im­prove­ment of fi­bro­sis and NASH.

The read­out sur­prised not on­ly be­cause of oth­er com­pa­nies’ strug­gles in NASH, but al­so be­cause of the his­to­ry of the drug it­self. It had al­ready failed the year pri­or in the rare fi­bro­sis dis­ease sys­temic scle­ro­sis. And a drug with a sim­i­lar mech­a­nism at Gen­fit had just failed one of the largest ever NASH stud­ies, trig­ger­ing sig­nif­i­cant lay­offs and prompt­ing the fel­low French biotech to ex­it the field en­tire­ly.

It’s dif­fi­cult to dis­cern what the dif­fer­ence was yet, though In­ven­ti­va notes that their drug ac­ti­vat­ed all of a re­cep­tor known as PPAR, while Gen­fit’s com­pound on­ly ac­ti­vat­ed PPAR al­pha and delta.

The win was enough to vault In­ven­ti­va to a $108 mil­lion IPO the fol­low­ing month, amid a run of pan­dem­ic biotech pub­lic of­fer­ings — a raise that val­ued the com­pa­ny at over $500 mil­lion. The com­pa­ny still has to meet with the FDA to dis­cuss the Phase II re­sults be­fore they can launch what they want to be a piv­otal Phase III tri­al in the first half of 2021, but the break­through des­ig­na­tion has giv­en CEO and co-founder Frédéric Cren con­fi­dence ahead of the dis­cus­sions.

“Ahead of our end of Phase IIb meet­ing with the FDA lat­er this year, the Break­through Ther­a­py des­ig­na­tion for lan­i­fi­bra­nor is a fan­tas­tic achieve­ment and a reg­u­la­to­ry recog­ni­tion of the sig­nif­i­cant clin­i­cal ben­e­fits lan­i­fi­bra­nor could pro­vide to NASH pa­tients as shown in our re­cent NA­TIVE Phase IIb clin­i­cal tri­al,” he said.

So­cial: Frédéric Cren, In­ven­ti­va CEO (In­ven­ti­va via YouTube)

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Like the flu vac­cine every year, the FDA could move quick­ly on a vari­ant-tar­get­ed Covid vac­cine

In the same way that the FDA signs off on flu vaccines every year without requiring large clinical trials to measure their efficacy, the FDA may employ a similar strategy in authorizing variant-focused versions of the mRNA vaccines.

As the world braces for more data on the latest variant Omicron, which may reduce vaccine efficacy, top vaccine developers like Moderna and Pfizer-BioNTech have promised they can pull together a new vaccine targeted against a specific Covid variant in about 100 days. Since Omicron emerged last week, Pfizer-BioNTech, Moderna and J&J have all said they’ve begun work on Omicron-specific vaccines, if needed.

More man­u­fac­tur­ing is­sues: Fen­nec preps for sec­ond CRL for po­ten­tial hear­ing loss drug

Shares of Fennec Pharmaceuticals stock were cut almost in half early Monday as the company said manufacturing issues caused another FDA rejection of its reformulated version of sodium thiosulfate, which is intended to help kids who lose hearing due to chemo treatment.

The biotech had resubmitted an NDA for the drug to treat platinum-based, chemo-related ototoxicity in young children earlier this year. The first NDA was denied by the FDA last year, with the agency citing manufacturing issues with the biotech’s supplier.

Troy Wilson, Kura CEO

UP­DAT­ED: FDA hits the red light on an ear­ly-stage AML study af­ter a pa­tient dies

The FDA has slapped a clinical hold on the early-stage program for one of Kura Oncology’s cancer drugs following a patient’s death in a clinical trial.

The biotech $KURA reported early Wednesday that the Phase Ib study of KO-539 for acute myeloid leukemia would be halted, suspending enrollment, while researchers and the FDA probed the death. Patients already on the drug can continue taking it.

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Róbert Wessman, Alvogen CEO

Biotech bil­lion­aire Róbert Wess­man en­gi­neers $450M deal for Alvo­gen sub­sidiaries

Alvogen is handing off two of its subsidiaries to CEO Róbert Wessman and his healthcare investment firm Aztiq — who has now tied the two together in a massive biobucks deal.

In an alliance with Thailand’s PTT Group subsidiary Innobic, the two companies signed an agreement last week to buy a 100% stake in Alvogen Emerging Market Holdings Limited (AEMH) for $475 million from Alvogen, buying out shareholders such as CVC Capital Partners and Singapore’s Temasek. And now, the group is the majority shareholder of Alvogen’s former Asian subsidiary Lotus Pharmaceuticals and the only shareholder of Alvogen Malta, the owner of B2B pharma Adalvo.

Giovanni Caforio, Bristol Myers Squibb CEO (Pablo Martinez Monsivais/AP Images)

Amid JAK de­ba­cle, Bris­tol My­ers set­tles in for FDA's long re­view of po­ten­tial first TYK2 drug

Bristol Myers Squibb has $4 billion hopes for its late-stage TYK2 inhibitor deucravacitinib, but the FDA’s recent negative review for the JAK inhibitor class has dampened hopes somewhat. Now, the agency will get its first good look at TYK2, and Bristol Myers will have to wait and hold its breath.

The FDA has set a target review date of Sept. 10, 2022, for deucravacitinib, a potential first-in-class oral inhibitor for the TYK2 signaling pathway in psoriasis that would be a challenger to the controversial JAK inhibitors, the drugmaker said Monday.

Shankar Musunuri, Ocugen CEO

Ocu­gen hits an­oth­er snag in bring­ing its Bharat Biotech-part­nered Covid-19 vac­cine to the US

Back in July, Ocugen and Bharat Biotech unveiled some Phase III data suggesting their Covid-19 vaccine, Covaxin, was 77.8% effective at preventing overall disease in India. They’re now looking to launch an immuno-bridging study to see if those numbers hold up in the US — but on Friday, the FDA said not so fast.

Regulators have placed a clinical hold on the partners’ IND, Ocugen shared on Friday. Ocugen’s stock $OCGN sank 9% on the news Friday, but was up almost 7% in pre-market trading on Monday.