Days af­ter In­ter­cept re­jec­tion, Akero surges on ‘un­prece­dent­ed‘ NASH da­ta

A year and a half af­ter scor­ing a $70 mil­lion Se­ries B and a top Gilead ex­ec­u­tive as CEO, Akero Ther­a­peu­tics has an­nounced new da­ta on their NASH drug. And with the field still reel­ing from a sur­prise FDA re­jec­tion this week, the news was enough to send their stock surg­ing.

Akero had al­ready said in March that its lead drug had beat­en place­bo in its Phase II tri­al, re­duc­ing liv­er fat by 14% in the high­est dose group com­pared to 0.3% in place­bo, ac­cord­ing to MRI scans. But al­though NASH is an obe­si­ty-re­lat­ed con­di­tion and re­sults from fat­ty buildup in the liv­er, the re­al im­me­di­ate ques­tion for any ther­a­py is whether it can re­solve the fi­bro­sis and in­flam­ma­tion that re­sults from that buildup. Those da­ta re­quire biop­sy­ing the pa­tients, a longer and more in­va­sive process that was fur­ther com­pli­cat­ed by a pan­dem­ic.

Now the biop­sies are in: Of the 40 pa­tients in the tri­al who re­spond­ed to treat­ment — an old Am­gen drug known as efrux­ifer­min — and were biop­sied, 48% saw at least a one-stage im­prove­ment in fi­bro­sis with­out any wors­en­ing on NAS, a score that mea­sures in­flam­ma­tion and oth­er bi­o­log­i­cal mark­ers of dis­ease. Ad­di­tion­al­ly, 48% of pa­tients saw their NASH re­solve with­out fi­bro­sis wors­en­ing. Near­ly a third saw a 2-stage im­prove­ment in fi­bro­sis with­out NAS wors­en­ing. There was al­so a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in weight loss for the high treat­ment arm.

Now what pre­cise­ly does all those da­ta mean?

In­vestors ap­peared to take it as a clear pos­i­tive, par­tic­u­lar­ly af­ter the FDA re­ject­ed what would have been the first specif­i­cal­ly ap­proved NASH drug on Mon­day, and its de­vel­op­er, In­ter­cept, saw its stock crash. Akero’s stock was up near­ly 40% pre-mar­ket Wednes­day, from $24.92 to $34.42 per share.

An­a­lysts, too, were bull­ish. Peg­ging a tar­get price at $48, Jef­feries’ Michael Yee called it “best-in-class NASH da­ta so far,” with “the best fi­bro­sis re­sults and strong ben­e­fits across meta­bol­ic and di­a­betes com­po­nents.” Ever­core ISI’s Josh Schim­mer said it was “an un­prece­dent­ed ef­fect on fi­bro­sis im­prove­ment and NASH res­o­lu­tion.” He pegged the stock at $80.

The tone from the com­pa­ny was sim­i­lar­ly up­beat. An­drew Cheng, the ex-Gilead ex­ec­u­tive who came over as CEO, said the da­ta “ex­ceed­ed our ex­pec­ta­tions.”

Still, the cen­tral ques­tion raised by In­ter­cept’s sur­prise re­jec­tion re­mains unan­swered: What, pre­cise­ly, does the FDA con­sid­er to be a good bar for ef­fec­tive­ness in NASH?

In lieu of stronger but nec­es­sar­i­ly longer term goals such as sur­vival or the num­ber of pa­tients who reach cir­rho­sis, com­pa­nies, with FDA guid­ance, have so far fo­cused on two end­points: im­prov­ing fi­bro­sis with­out NASH wors­en­ing or re­solv­ing NASH with­out fi­bro­sis wors­en­ing.

In­ter­cept was the first com­pa­ny to hit on one of those in a Phase III tri­al, al­though they missed on the oth­er. Their re­jec­tion means that just hit­ting one end­point won’t be enough.

Ad­di­tion­al­ly, to­day’s da­ta are on­ly a sec­ondary analy­sis of re­spon­ders, and don’t prove a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in those end­points com­pared to place­bo. Akero will need a larg­er piv­otal tri­al for that, one that could be the next big study for the field.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

So it was for Biohaven $BHVN on MLK Monday, as the biotech reported on the holiday that their Phase II/III Alzheimer’s study for troriluzole flunked both co-primary endpoints as well as a key biomarker analysis.

The drug — a revised version of the ALS drug riluzole designed to regulate glutamate — did not “statistically differentiate” from placebo on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).  The “hippocampal volume” assessment by MRI also failed to distinguish itself from placebo for all patients fitting the mild-to-moderate disease profile they had established for the study.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

Dan Skovronsky, Eli Lilly CSO (Lilly via Facebook)

Eli Lil­ly tees up dis­cov­ery pact worth more than $1.6B with Merus for T cell-fo­cused bis­pe­cif­ic an­ti­bod­ies

Under science chief Dan Skovronsky, Eli Lilly has taken some big swings at next-gen therapies, including trying to find the next big thing in oncology. Now, after one early failure in the field, Lilly is going back to the bispecific antibody well with a new deal with a Dutch biotech.

Lilly will pay $40 million upfront with an additional $20 million equity stake in Merus NV to identify and develop three bispecific antibodies looking to engage the CD3 antigen on T cells and redirect immune cells, the Indianapolis pharma giant said Tuesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,100+ biopharma pros reading Endpoints daily — and it's free.

Andrew Allen (Gritstone)

As coro­n­avirus vari­ants trig­ger new alarms, the NIH is putting an un­der-the-radar ‘next-gen’ vac­cine in­to PhI

Over the past year, the world has been transfixed by the development of new vaccines to fight SARS-CoV-2. In a frenzy of activity, the new mRNA approach has delivered pioneering emergency approvals in record time. And with some setbacks, the more traditional big players are coming along with added jabs as the most affluent nations in the world begin to vaccinate large portions of their populations.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

The IPO queue adds 5 more biotechs hop­ing to ring in 2021 by blitz­ing Nas­daq

Following a record year for IPOs — in terms of both proceeds and count — there’s already a long lineup of biotechs ready to jump onto Nasdaq in the new year. The companies are likely looking for much higher raises than they initially projected on their S-1s. Now it’s time to see if investors are still hungry for another round of biotech stocks.

Sana helped set the pace early on, as its founders look to divvy up a fortune from their IPO. And late last week 5 more biotechs crowded in, looking to pick up the pace where 2020 left off. Here they are:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,100+ biopharma pros reading Endpoints daily — and it's free.

Janet Woodcock (AP Images)

Janet Wood­cock is in the run­ning for FDA com­mis­sion­er — what does that mean for the agen­cy's fu­ture?

Just a day after reports emerged that Janet Woodcock will serve as interim chief of the FDA, word has gotten out that she is also in the running for the permanent job.

The decision, as the initial wave of reactions suggest, could have dramatic implications for where the agency is headed in the next four years — if not beyond.

Woodcock, the longtime CDER director, is being vetted alongside former FDA principal deputy commissioner Joshua Sharfstein, Bloomberg reported. Already tapped as acting head of the agency, she’s set to take over from Stephen Hahn right after Biden’s inauguration next week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,100+ biopharma pros reading Endpoints daily — and it's free.

News brief­ing: Beam bags a $260M pri­vate place­ment; mi­Ra­gen re­brands to Virid­i­an Ther­a­peu­tics

Agios vet John Evans has demonstrated how to raise big money for a little biotech.

The Beam Therapeutics CEO — and ARCH partner — has pieced together a $260 million private placement from a group of backers that includes Perceptive Advisors, Farallon Capital, Casdin Capital, Redmile Group and Cormorant Asset Management. And there are 3 main goals they’ll pursue with it: clinical development, strategic partnerships and general corporate purposes.

As­traZeneca keeps the ball rolling on Dai­ichi-part­nered En­her­tu, pick­ing up 2nd in­di­ca­tion in gas­tric can­cer

AstraZeneca’s big gamble on Daiichi Sankyo’s antibody-drug conjugate Enhertu has already paid off with a big approval in breast cancer more than a year ago. But the partners have big plans for their blockbuster in the making, and a new nod in gastric cancer will raise their spirits even higher.

The FDA on Friday approved Enhertu to treat locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma in patients who have previously undergone at least one round of treatment with a Herceptin-based regimen, AstraZeneca said in a release.