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)

Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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Un­fazed by PhII miss, Roche ush­ers Prothena's Parkin­son's drug in­to late-stage tri­al — a $60M move

Prothena’s prasinezumab may not have met the primary endpoint in Phase II, but its partners at Roche are seeing enough to move it into a late-stage trial for Parkinson’s disease.

The Phase IIb will build on the Phase II PASADENA study, adding a subgroup of early Parkinson’s patients on stable levodopa therapy to the population.

It’s a significant milestone for a $600 million deal that dates back to 2013, as dosing of the first patient — expected next year — will trigger a $60 million milestone payment to Prothena.

CEO Grace Colón (InCarda)

Look­ing to re­pur­pose an old drug to treat ir­reg­u­lar heart­beats, In­Car­da rais­es $30M in first Se­ries C close

A little less than two years after completing its $42 million Series B round, InCarda has returned to the venture well.

The San Francisco-based biotech announced the first portion of its Series C on Wednesday, pulling in $30 million in new funding. Most of the money will give enough runway for InCarda’s InRhythm program, an inhaled therapeutic aiming to treat sudden episodes of irregular heartbeats, through its Phase II trials and prepare it for Phase III.

RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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Covid-19 roundup: As­traZeneca could soon re­sume US vac­cine tri­als; Pfiz­er's dis­tri­b­u­tion plan in­volves spe­cial ship­ping box­es, no whole­salers 

AstraZeneca’s Covid-19 vaccine trial could resume in the US later this week, according to a Reuters report.

Experimental dosing of the candidate came screeching to a halt in September, when a participant in the UK suffered what’s believed to be the spinal inflammatory condition transverse myelitis. Trials have already resumed in the UK, Brazil, India, Japan and South Africa — and four anonymous sources told Reuters that a green light from the US could come as early as this week.

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Steve Chen, Cellis Therapeutics president and CMO (Cellics)

UC San Diego spin­out award­ed up to $15M for nanosponge de­signed to soak up sep­sis-caus­ing tox­ins

CARB-X, a global partnership looking to spur the development of new antibacterial drugs, is awarding Cellics Therapeutics $3.94 million to do what president and CMO Steve Chen calls “looking at traditional drug development upside down.”

Instead of going after a target directly — in this case bacterial toxins and inflammatory cytokines that cause sepsis — Cellics researchers “flip it around” to examine the host cells being attacked. The UC San Diego spinout then creates what it calls “nanosponges” — nanoparticles cloaked in the fragments of macrophage cell membranes. Chen says the “sponges” are designed to trap the sepsis-causing endotoxins and cytokines on their cell membranes, neutralizing them.