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.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.