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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

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Zhi Hong, Brii Biosciences CEO

Brii Bio­sciences stops man­u­fac­tur­ing Covid-19 an­ti­body com­bo, plans to with­draw EUA re­quest

Brii Biosciences said it will stop manufacturing its Covid-19 antibody combination, sold in China, and is working to withdraw its emergency use authorization request in the US, which it started in October 2021.

The Beijing and North Carolina biotech commercially launched the treatment in China last July but is now axing the work and reverting resources to other “high-priority programs,” per a Friday update. The focus now is namely hepatitis B viral infection, postpartum depression and major depressive disorders.

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Sergio Traversa, Relmada Therapeutics CEO

Rel­ma­da makes 'crit­i­cal changes' to PhI­II tri­al to try and save de­pres­sion drug

Relmada Therapeutics is making changes to its Phase III study of its lead drug for major depressive disorder, in an attempt to avoid problems with a prior trial that showed little difference between the drug and a placebo.

That failure in October wiped 80% from Relmada’s stock price, and was followed by another negative readout a few months later. In both cases, the company said that there had been trial sites that were associated with what it called surprising placebo effects that skewed the results compared with the drug, REL-1017.

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Peter Hecht, Cyclerion Therapeutics CEO

Hard pressed for cash, Cy­cle­ri­on looks for help fund­ing rare dis­ease drug

Cyclerion Therapeutics may have the design of a Phase IIb study ready to go, but it’s scrambling for a way to fund it.

The company said in a press release that it’s “actively evaluating the best combination of capital, capabilities, and transactions available to it to advance the development of zagociguat,” its lead candidate for a rare, genetic mitochondrial disease known as MELAS.

In a separate SEC filing, Cyclerion once again flagged “substantial doubt about (its) ability to continue as a going concern.” As of the end of 2022, it had cash and cash equivalents of only $13.4 million.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Geoff McDonough, Generation Bio president and CEO

Mod­er­na part­ners on non-vi­ral gene ther­a­py with Gen­er­a­tion Bio af­ter swing­ing gene edit­ing deals

Moderna has inked a five-year partnership with gene therapy biotech Generation Bio, it announced Thursday morning, wading deeper into the genetic medicines space as it navigates beyond its vaccine work.

Moderna will pay Generation Bio $40 million upfront and invest another $36 million into the gene therapy biotech. In exchange, Moderna can license Generation Bio’s non-viral gene therapy platforms for two immune cell programs and two liver programs, with an option for a fifth program. Moderna will fund all the research work under the partnership, and could be on the hook for milestone, fee and royalty payments totaling up to $1.8 billion, a company spokesperson tells Endpoints News.

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Paul Song, NKGen Biotech CEO

NK cell ther­a­py-fo­cused biotech eyes SPAC deal

A small, Santa Ana-based biotech created in 2017 is looking to enter a SPAC deal as it lays out plans to begin trials in its lead cell therapy candidates and bring on new executives.

Graf Acquisition Corp. IV and NKGen Biotech announced Thursday, with few other details, that the two companies signed a non-binding letter of intent to “pursue a business combination.” Graf Acquisition II and III withdrew their IPOs last year.

In­cyte hit by CRL on ex­tend­ed-re­lease JAK tablets, mud­dy­ing plans for Jakafi fran­chise ex­pan­sion

The FDA has rejected Incyte’s extended-release formulation of ruxolitinib tablets, in a surprise setback for the company’s plans to build on its blockbuster Jakafi franchise.

The ruxolitinib XR tablets are designed to be taken once a day, whereas Jakafi is indicated for twice daily dosage (although some patients can take it once daily).

According to Incyte, the FDA acknowledged in its complete response letter that the study submitted in the NDA “met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval.”