John McHutchison, Assembly Biosciences CEO (Getty Images)

As­sem­bly Bio's he­pati­tis B pro­gram flops as a po­ten­tial cure in PhII, send­ing shares spi­ral­ing

Look­ing for a he­pati­tis B cure, As­sem­bly Bio­sciences $ASMB has struck out in a Phase II.

The South San Fran­cis­co-based com­pa­ny an­nounced Thurs­day af­ter­noon that its lead ex­per­i­men­tal drug ve­bi­corvir, in com­bi­na­tion with nu­cle­o­side ther­a­py, could not keep pa­tients dis­ease-free af­ter stop­ping treat­ments. In to­tal, 39 of the 41 in­di­vid­u­als in the open-la­bel study re­lapsed, as the reg­i­men failed to achieve a mean­ing­ful sus­tained vi­ro­log­ic re­sponse.

In­vestors did not take too kind­ly to the news, ham­mer­ing the biotech’s share prices af­ter the bell. As­sem­bly’s stock dropped as much as 40% on Thurs­day evening but has since lev­eled off to down about 35%.

The He­pati­tis B pa­tients in­volved in As­sem­bly’s Phase II gen­er­al­ly re­quire treat­ments for the rest of their lives. As­sem­bly’s the­o­ry went that if they could show enough of a pro­longed re­sponse af­ter tak­ing pa­tients off the pro­gram, which is sep­a­rate­ly be­ing stud­ied as a chron­ic sup­pres­sive ther­a­py, then it could ef­fec­tive­ly func­tion as a cure.

In or­der to find that out, As­sem­bly treat­ed their pa­tients with the com­bi­na­tion ther­a­py for 12 to 18 months. Fol­low­ing that pe­ri­od, re­searchers stopped the treat­ments and eval­u­at­ed the 41 pa­tients every four weeks to see whether or not the com­bo was ef­fec­tive enough at pre­vent­ing a re­lapse af­ter an ex­tend­ed pe­ri­od of time.

But 33 of the 41 pa­tients saw their he­pati­tis B re­turn af­ter the first four-week eval­u­a­tion. By the 16-week mark, an­oth­er six pa­tients re­lapsed. As­sem­bly had been look­ing for an SVR rate of at least 15% af­ter 24 weeks, but Thurs­day’s re­sults equate to a rate of less than 5%.

Though Thurs­day’s re­sults are in­deed a neg­a­tive, As­sem­bly’s com­bo still has po­ten­tial as a chron­ic ther­a­py, Baird’s Bri­an Sko­r­ney wrote in a note to in­vestors. See­ing that the near-term cure play is now “off the ta­ble,” Sko­r­ney says As­sem­bly can ef­fec­tive­ly piv­ot to­ward that path, but notes the up­side is much more lim­it­ed.

“Al­though the busi­ness op­por­tu­ni­ty for a chron­ic ther­a­py for He­pati­tis B is much less at­trac­tive than a cu­ra­tive reg­i­men, we still see it as a rea­son­able busi­ness,” Sko­r­ney wrote.

Should As­sem­bly take that route, Sko­r­ney pre­dicts the ther­a­py could reach any­where be­tween $500 mil­lion and $1 bil­lion in an­nu­al sales.

As­sem­bly has pre­vi­ous­ly tak­en steps to turn that in­to a re­al­i­ty, ink­ing a $540 mil­lion deal with BeiGene in Ju­ly to take the ve­bi­corvir and nu­cle­o­side com­bo in­to a Phase III for chron­ic sup­pres­sion of He­pati­tis B. The tri­al is ex­pect­ed to be­gin some­time in the first half of next year, and will in­clude a group of pa­tients who have seen on­ly par­tial vi­ral sup­pres­sion af­ter a year or more of nu­cle­o­side monother­a­py.

The com­pa­ny is al­so look­ing in­to whether ve­bi­corvir could still cure he­pati­tis B in a triple ther­a­py con­coc­tion. In Au­gust, As­sem­bly hooked on­to a deal with Ar­bu­tus Bio­phar­ma and plans to launch the first Phase II next year that com­bines ve­bi­corvir, nu­cle­o­side treat­ment and Ar­bu­tus’ RNAi ther­a­peu­tic for the dis­ease. Sko­r­ney notes the com­pa­nies are still in the ear­ly de­vel­op­men­tal stages, how­ev­er.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,200+ biopharma pros reading Endpoints daily — and it's free.

David Reese, Amgen R&D chief

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,200+ biopharma pros reading Endpoints daily — and it's free.

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,200+ biopharma pros reading Endpoints daily — and it's free.

Anna Protopapas, Mersana CEO

In $1.36B biobuck deal with GSK, Mer­sana touts 'biggest pre­clin­i­cal ADC deal ever'

Days after Enhertu reeled in another FDA nod, with the first-ever green light for HER2-low breast cancer, another antibody drug conjugate biotech claims it has secured the largest preclinical ADC pact to date for a single asset.

AstraZeneca and Daiichi Sankyo made waves with their nearly $7 billion collaboration back in spring 2019, but at that point, Enhertu was already nearing the FDA’s doors with clinical data. The latest ADC tie-up to enter the biopharma fray centers around a preclinical asset, Mersana Therapeutics’ XMT-2056.

Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,200+ biopharma pros reading Endpoints daily — and it's free.

FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, just two weeks after submitting a supplemental BLA. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

Endpoints Premium

Premium subscription required

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