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.

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III Voyage trial before they give a judgment.

Io­n­is, Akcea boost­ed by a pos­i­tive PhII for their No­var­tis castoff car­dio drug — and they plan to push ahead in­to piv­otals

Late last year Novartis abandoned a cardio drug from Ionis’ spinoff Akcea just after the pharma giant snapped up inclisiran, going the RNAi way in guarding against heart disease in the $9.7 billion Medco buyout.

Now the pharma goliath — which is headed down the PCSK9 road with a drug it believes can be used in a mass population — can get a clearer picture of just what they gave up.

Akcea $AKCA and the mother company $IONS put out a statement early Wednesday saying that their Phase II study of AKCEA-APOCIII-LR delivered solid efficacy data, with the high dose clearly outperforming placebo in significantly reducing triglycerides as a means to cutting the risk of cardiovascular disease. In addition, investigators concluded that the drug slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting “good” HDL levels.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.