In a stun­ning about face, the FDA is now wel­com­ing the new drug ap­pli­ca­tion from Alk­er­mes it re­ject­ed 2 weeks ago

Some­body at the FDA just got a rude wake up call.

Just two weeks af­ter the FDA in­vit­ed Wall Street to pum­mel Alk­er­mes $ALKS by re­fus­ing to even ac­cept its ap­pli­ca­tions for the de­pres­sion drug ALKS-5461, the biotech says that the agency has sud­den­ly de­cid­ed to sim­ply change its mind.

Ac­cord­ing to Alk­er­mes, the stun­ning about face came af­ter the com­pa­ny “clar­i­fied cer­tain as­pects of the NDA sub­mis­sion. No ad­di­tion­al da­ta or analy­ses were sub­mit­ted by Alk­er­mes to FDA.”

Alk­er­mes shares im­me­di­ate­ly shot up 20%, re­gain­ing $1.3 bil­lion of its mar­ket cap. But it couldn’t hold on to that, though, drop­ping to an 8% gain mid-morn­ing. Its PDU­FA date was set for Jan­u­ary 31, 2019.

Alk­er­mes said in ear­ly April that the FDA was de­mand­ing that the com­pa­ny con­duct ad­di­tion­al tri­als of 5461, a move that ham­mered the com­pa­ny’s share price as an­a­lysts pon­dered the years of work and ex­pense in tak­ing an­oth­er risky shot at gain­ing pos­i­tive clin­i­cal da­ta.

The com­pa­ny was throw­ing the dice on its ap­pli­ca­tion when it first filed, hop­ing to per­suade the FDA that its one pos­i­tive piv­otal study along with ad­di­tion­al da­ta would out­weigh the two failed tri­als that tar­nished the drug. That would not have met the agency’s long es­tab­lished stan­dard for two pos­i­tive stud­ies, but as I’ve writ­ten ear­li­er the FDA has been ratch­et­ing down its hur­dles to get more drugs ap­proved.

The change up marks an­oth­er sign of the dra­mat­ic shift in the FDA’s stance on drug ap­pli­ca­tions and its stan­dards for re­views, rais­ing some ma­jor ques­tions for the in­dus­try as well as con­sumers. Since Scott Got­tlieb be­came com­mis­sion­er in 2017 af­ter he was nom­i­nat­ed for Pres­i­dent Don­ald Trump with a man­date to speed new drug ap­provals, the agency re­versed it­self on three key drug re­jec­tions for Eli Lil­ly, Ther­a­peu­tic­sMD and Am­i­cus, wav­ing off its ear­li­er de­mands for more work.

None of these re­ver­sals car­ry a guar­an­tee of an ap­proval, but they do re­flect changes in di­rec­tion that all drug de­vel­op­ers will pay close at­ten­tion to.

Bar­clays summed it up this way:

Giv­en the po­lit­i­cal na­ture of the cur­rent FDA ad­min­is­tra­tion, we could see a sce­nario where nor­mal-course re­view for ALKS-5461 felt more “ap­pro­pri­ate” than con­tro­ver­sy raised by an RTF, es­pe­cial­ly con­sid­er­ing the prod­uct’s pri­or Fast Track des­ig­na­tion and med­ical need for in­no­va­tion with­in the in­di­ca­tion. How­ev­er, we con­tin­ue to feel ALKS is long from out of the woods on ALKS-5461 and will need to con­tin­ue to en­gage with FDA dur­ing re­view with po­ten­tial for the on­go­ing Phase 3 to play a role in any po­ten­tial ap­proval or re­view de­ci­sion.

Who at the FDA over­ruled the de­ci­sion to re­ject Alk­er­mes’ drug ap­pli­ca­tion? And why?

The agency, bound by strict rules of si­lence when it comes to com­ment­ing on com­pa­nies and drugs out­side a care­ful­ly reg­u­lat­ed set of pub­lic dis­clo­sures, de­clined com­ment — as they al­ways do.

Craig Hop­kin­son

Craig Hop­kin­son, chief med­ical of­fi­cer and se­nior vice pres­i­dent of med­i­cines de­vel­op­ment and med­ical af­fairs at Alk­er­mes had this to say:

“We will con­tin­ue to en­gage with the FDA through­out the re­view process, as we work to bring this im­por­tant med­i­cine to pa­tients.”

Im­age: Alk­er­mes CEO Richard Pops at an End­points event, Jan­u­ary 2017. END­POINTS NEWS

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

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