Safety threat forces Enanta to scrap HBV trials — sending discovery team back to drawing board

Jay Luly, Enanta CEO (via YouTube)

A Mass­a­chu­setts biotech will dis­con­tin­ue the de­vel­op­ment of its oral drug in­tend­ed to treat pa­tients suf­fer­ing from chron­ic he­pati­tis B in­fec­tions, the com­pa­ny said Thurs­day.

Enan­ta Phar­ma­ceu­ti­cals will no longer de­vel­op EDP-721. The news comes af­ter safe­ty sig­nals were seen in healthy par­tic­i­pants in a Phase I tri­al af­ter they were ad­min­is­tered the drug, and de­spite a clean safe­ty pro­file demon­strat­ed in pre­clin­i­cal tri­als.

‘Pa­tient safe­ty is our top pri­or­i­ty, and we have there­fore de­cid­ed to dis­con­tin­ue fur­ther de­vel­op­ment of this com­pound,’ said CEO Jay Lu­ly. ‘We are com­mit­ted to de­vel­op­ing a func­tion­al cure for chron­ic he­pati­tis B pa­tients, and re­main con­fi­dent in EDP-514, our HBV core in­hibitor, which has demon­strat­ed safe and ro­bust an­tivi­ral ac­tiv­i­ty in Phase 1b stud­ies of viremic and NUC-sup­pressed pa­tients with chron­ic HBV in­fec­tion.

Enan­ta will ad­vance its HBV pro­gram af­ter fur­ther dis­cov­ery ef­forts, Lu­ly said.

He­pati­tis B is a vi­ral in­fec­tion that can at­tack the liv­er and cause both acute and chron­ic dis­ease. It is most typ­i­cal­ly trans­mit­ted from moth­er to child in birth and de­liv­ery, as well as through oth­er bod­i­ly flu­ids. An es­ti­mat­ed 290 mil­lion peo­ple around the world have chron­ic HBV in­fec­tions.

Enan­ta is cur­rent­ly de­vel­op­ing can­di­dates to tar­get res­pi­ra­to­ry syn­cy­tial virus, HBV and Covid-19. Its R&D ef­forts are fund­ed through roy­al­ties from its he­pati­tis C virus prod­ucts de­vel­oped along­side Ab­b­Vie.

Ear­ly last month, the com­pa­ny of­floaded in-house de­vel­op­ment of its two FXR ag­o­nist NASH drugs, EDP-305 and fol­low-up can­di­date EDP-297, and said it would move to an out-li­cens­ing strat­e­gy af­ter the ear­ly da­ta showed lit­tle chance of so­lo suc­cess for ei­ther drug. Baird an­a­lyst Bri­an Sko­r­ney called the de­ci­sion ‘in­cre­men­tal­ly pos­i­tive,’ re­mark­ing that Enan­ta could fo­cus its work on ef­forts in Covid-19, RSV and HBV, while avoid­ing the long, wind­ing road that comes along with NASH. But the lat­est set­back will send the com­pa­ny back to the draw­ing board again.

‘We be­lieve that the mul­ti­ple mech­a­nisms in de­vel­op­ment for NASH to­day, which re­flect the com­plex patho­phys­i­ol­o­gy of this dis­ease, make it like­ly that a com­bi­na­tion ap­proach with FXR ag­o­nists will ul­ti­mate­ly pro­vide the op­ti­mal treat­ment reg­i­men for pa­tients,’ Lu­ly said in a state­ment.

Enan­ta did an­nounce pos­i­tive da­ta from its Phase Ib study of EDP-514 to treat NUC-sup­pressed chron­ic HBV pa­tients. The tri­al showed that it was safe and well-tol­er­at­ed, and the da­ta sup­port a once-dai­ly oral dos­ing reg­i­men.

For years, paper-based processes and individual point solutions dominated the clinical research landscape, and patient participation in clinical trials was largely an in-person engagement. But when the COVID-19 pandemic took a stronghold, traditional clinical trial methods emerged as inadequate, putting clinical trials and the life sciences industry at a crossroads. Practically overnight, the industry had to rapidly shift to decentralized clinical trial methods, while maintaining data quality and regulatory compliance.

Douglas Fambrough, Dicerna CEO (Dicerna via YouTube)

Early this year researchers at Novo Nordisk were beaming as they announced the first drug identified in their RNAi alliance with Dicerna was headed into the clinic. And now they’re coming back for the whole thing.

This morning the Copenhagen-based pharma giant put out word that it is buying Dicerna $DRNA — an RNAi pioneer that has had its up and downs over the years — for $3.3 billion. Novo is paying $38.25 a share — an 80% premium.

Unlock this story instantly and join 123,700+ biopharma pros reading Endpoints daily — and it’s free.

Mathai Mammen, head of R&D for J&J’s Janssen unit (Rob Tannenbaum)

Last week, J&J took a step familiar to other pharma conglomerates in spinning out its consumer business to focus on R&D, but offered few details on what that might look like. But on Thursday, the company followed up with the scoop, and it’s making some bold predictions.

Over the course of a two-plus hour presentation on its pharmaceutical business, execs outlined their strategy for the new, slimmer J&J, promising investors it will file about 14 drugs for approval through 2025. Across all these drugs, J&J said it expects $4 billion average peak annual sales, and five could top the $5 billion mark.

Unlock this story instantly and join 123,700+ biopharma pros reading Endpoints daily — and it’s free.

The Congressional Budget Office on Thursday evening made abundantly clear that President Biden’s push to allow Medicare to negotiate prescription drug prices for a limited number of single source drugs will only make a minor dent in the pocketbook of the biopharma industry, and likely cost industry just 10 new drugs over the next 30 years.

The provisions are part of a huge, $1.8 trillion spending package that the Democrats and Biden have been pushing for all summer. The bill is expected to pass this morning in the House.

In a surprise setback, Merck has slammed the brakes on the development of an experimental HIV drug — including a Phase II trial — after investigators flagged a drop in immune cell counts that an external committee determined was related to treatment.

The Phase II study that first sounded the alarm, dubbed IMAGINE-DR, was testing the once-weekly combination of MK-8507 (a non-nucleoside reverse transcriptase inhibitor) and islatravir, or ISL, a nucleoside reverse transcriptase translocation inhibitor.

Gilead is going all in — hook, line and sinker — on its oncology alliance with Arcus. And they are going for broke.

The big biotech unveiled a deal that now delivers $725 million in opt-in payments covering the clinical development programs for Arcus, ranging from their closely watched anti-TIGIT programs for domvanalimab and AB308 to etrumadenant (the A2a/A2b adenosine receptor antagonist) and quemliclustat, the small molecule CD73 inhibitor. Gilead will also cover half of the development costs, handing Terry Rosen’s biotech a deal that gives them a clear cash runway to achieving all its goals in oncology.

Unlock this story instantly and join 123,700+ biopharma pros reading Endpoints daily — and it’s free.

Kathryn Corzo — an oncology veteran and the program head behind Sanofi’s multiple myeloma monoclonal antibody isatuximab — is now in the C-suite.

The newest member at cell therapy player bit.bio as their COO, the longtime drug developer left Takeda (where she served, in turn, as the head of oncology cell therapy and then a partner in its venture arm) to join the small biotech. For Corzo, bit.bio presented a unique opportunity to try and solve issues that had been plaguing cell therapy — and one of the three reasons why she left Takeda.

The US Securities and Exchange Commission has launched a probe into claims that Cassava Sciences, an Austin-based drug developer, manipulated data key to its case for its experimental Alzheimer’s drug simufilam, the Wall Street Journal reported Wednesday.

The report comes just two days after Cassava in an SEC filing revealed that ‘certain government agencies’ had asked the biotech for documentation. It wasn’t clear which agencies were inquiring or what information they sought, and Cassava went out of its way to say the requests weren’t accusations of wrongdoing.

Unlock this story instantly and join 123,700+ biopharma pros reading Endpoints daily — and it’s free.

Michel Vounatsos (Biogen via YouTube)

RBC analyst Brian Abrahams is back with an update on the death of an Alzheimer’s patient on Biogen’s controversial aducanumab, and this time he says that there are solid reasons to believe that the event was likely drug related and may have been preventable.

Abrahams, a physician, notes that he obtained new information using FOIA, getting the ‘detailed case report’ about the aducanumab patient he was first to report on.

Unlock this story instantly and join 123,700+ biopharma pros reading Endpoints daily — and it’s free.
https://endpts.com/amidst-safety-concerns-enanta-ends-hbv-drug-trials-sending-discovery-team-back-to-drawing-board/