FDA’s in-house re­view of­fers bleak as­sess­ment of Epizyme’s tazeme­to­stat — but win or lose this can­cer drug may still have a fu­ture

Epizyme will have to over­come a tough as­sess­ment from the FDA’s in-house re­view team for their can­cer drug tazeme­to­stat if they ex­pect to make it to the mar­ket with an OK on ep­ithe­lioid sar­co­ma. But they $EPZM may well have the agency’s on­col­o­gy pan­el on their side, where there’s a built-in bias in fa­vor of even mar­gin­al new drugs when it comes to of­fer­ing physi­cians and pa­tients an­oth­er drug to choose from.

As the FDA notes, there’s not much da­ta to sup­port tazeme­to­stat as an ef­fec­tive drug for these cas­es of sar­co­ma. Pool­ing da­ta from 2 co­horts in their piv­otal study, they came out with a col­lec­tive over­all re­sponse rate of on­ly 13%. Out of 106 pa­tients, on­ly 2 ex­pe­ri­enced a com­plete re­sponse.

The ex­pert pan­el has to com­pare that po­ten­tial ben­e­fit with a litany of risks. Close to half the pa­tients ex­pe­ri­enced a grade 3 or 4 se­ri­ous ad­verse event. And there was this:

A to­tal of 23 (37%) pa­tients had a se­ri­ous AE (SAE). SAEs that oc­curred in ≥ 2 pa­tients were he­m­or­rhage and pleur­al ef­fu­sion (6.5%), dys­p­nea (5%), and cel­luli­tis and pain (3.2%). There were no fa­tal ad­verse events at­trib­ut­able to tazeme­to­stat. Al­though 34% of pa­tients re­quired a dose in­ter­rup­tion for tox­i­c­i­ty, dose re­duc­tions and dis­con­tin­u­a­tions of tazeme­to­stat for tox­i­c­i­ty were rare.

Al­so un­help­ful is tazeme­to­stat’s check­ered past. The biotech had a rough go last year when the FDA put tri­al re­cruit­ment on hold af­ter a young pa­tient de­vel­oped sec­ondary T-cell lym­phoma. And that fol­lowed their de­ci­sion to scrap a sep­a­rate pro­gram for dif­fuse large B-cell lym­phoma, DL­B­CL, af­ter con­clud­ing that it wouldn’t suc­ceed as a monother­a­py.

Jef­feries’ Michael Yee read the agency re­view and con­clud­ed that Epizyme had at best a 20% or 25% chance of an ap­proval, not­ing the FDA’s hes­i­tan­cy to call it on the risk/re­ward ra­tion.

(W)e could see FDA ask­ing EPZM to run a ran­dom­ized study, es­pe­cial­ly as LLY’s Lar­tu­vo was re­cent­ly pulled af­ter the drug failed its con­fir­ma­to­ry study in soft tis­sue car­ci­no­ma, (4) while Taz ap­pears well tol­er­at­ed, the risk of sec­ondary ma­lig­nan­cies re­mains un­clear (e.g. T-LBL) and that could be an “on-tar­get” ef­fect of Taz (this was the premise of the par­tial clin­i­cal hold in 2018). How­ev­er, we note in the ODAC di­vi­sion, the FDA is gen­er­al­ly more le­nient be­cause there are no ap­proved ther­a­pies, so FDA could still ap­prove Taz de­spite voic­ing cau­tious­ness.

For Yee, though, this is a bit of a sideshow. The re­al up­side for Epizyme is the larg­er fol­lic­u­lar lym­phoma field, where the biotech stands to make a po­ten­tial $500 mil­lion-plus in peak sales. So what­ev­er hap­pens dur­ing the pan­el re­view to­mor­row, he’ll still be hold­ing out hope for some­thing big­ger ahead.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Cy­to­ki­net­ics’ ALS drug fails PhI­II, leav­ing the biotech with a sin­gle late-stage prospect

Cytokinetics’ candidate for the muscle disease amyotrophic lateral sclerosis, or ALS, failed a Phase III trial, the Bay Area biotech announced Friday morning.

At a second interim analysis of the trial, an independent review committee recommended that Cytokinetics discontinue its COURAGE-ALS trial for reldesemtiv, as it “found no evidence of effect” compared to placebo on the primary or key secondary endpoints.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

CHMP gives thumbs-up for We­govy use in ado­les­cents, along with nine new drug rec­om­men­da­tions

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended nine drugs for approval this week while also giving thumbs up for six expanded indications, including Novo Nordisk’s approved obesity medication Wegovy for younger people. Wegovy is already approved as an obesity treatment in the EU for adults, and the new indication would allow prescriptions for adolescents aged 12 and older.

Austin biotech Mol­e­c­u­lar Tem­plates lays off more than 100 staffers as pipeline nar­rows

Molecular Templates is ridding itself of a Phase I HER2 asset and fine-tuning its pipeline to focus on three programs and a preclinical Bristol Myers Squibb collaboration. With the narrowed scope on its so-called engineered toxin bodies, the Austin, TX biotech is laying off about half of its staff.

That’s a little more than 100 employees, per an SEC filing. Molecular’s layoffs, approved by its board Wednesday, add to the dozens of pullbacks in the industry in the first three months of 2023.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Lu­pus drug de­vel­op­ment mar­ket heat­ing up, while FDA links with ad­vo­ca­cy group to fur­ther ac­cel­er­ate re­search

The long-underserved systemic lupus erythematosus (SLE) market is suddenly buzzing with treatment possibilities. Less than two years after AstraZeneca’s approval for Saphnelo — the first new SLE drug in a decade and joining just one other approved in GSK’s Benlysta – the pipeline of potential drugs numbers in the dozens.

Although most are very early stage — Spherix Global Insights estimates five in Phase II/III — the pharma R&D enthusiasm is catching on among doctors, patients and advocacy groups. On Wednesday, the Lupus Research Alliance and the FDA formed a novel private-public partnership called Lupus Accelerating Breakthroughs Consortium (Lupus ABC) to help advance lupus clinical trial success.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Green­Light re­ceives buy­out of­fer; Apol­lomics com­pletes SPAC merg­er

RNA biotech GreenLight Biosciences has been handed an offer for potential acquisition.

GreenLight said in a release that it has received a non-binding “indication of interest” from Fall Line Endurance Fund to acquire GreenLight’s capital stock for $0.60 per share in cash. The release said any potential agreement between the two parties would depend on certain conditions.

Through a special committee, the biotech will evaluate the offer but added there’s no certainty a deal will go forward. GreenLight will also not make any more announcements until a deal comes through or “otherwise determines” a statement is necessary.

TScan Therapeutics' departing CEO David Southwell and CSO/COO Gavin MacBeath

TCR up­start an­nounces CEO ex­it, with CSO now act­ing re­place­ment

A public T cell biotech’s chief executive has decided to leave the company.

TScan Therapeutics said Friday morning that CEO David Southwell stepped down earlier this week, leaving both his chief executive and board member roles. Filling in is Gavin MacBeath, the company’s CSO and COO. He became the acting CEO on Tuesday, and will continue to remain CSO and COO, TScan’s announcement read.

Aptinyx eval­u­ates fu­ture of the com­pa­ny fol­low­ing two failed tri­als, 60% lay­offs

This year has been tough for Aptinyx — two failed trials, a 60% cut in its workforce, and now the company has brought on a firm to help evaluate the future of the company.

The press release noted it’s working with the firm Ladenburg Thalmann as its financial advisor to assist in exploring and evaluating “strategic alternatives” — a process that a growing group of struggling biotechs has embarked on, sometimes ending in a merger, asset sale or wind-down.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.