Roy Baynes, Merck Research Laboratories CMO (file photo)

UP­DAT­ED: FDA says it needs a lit­tle more time to de­cide on Mer­ck­'s P2X3 for chron­ic cough

A few months ago, Mer­ck emerged as a clear leader among a group of drug­mak­ers rac­ing through the clin­ic with a new class of ther­a­pies for chron­ic cough. But it looks like the Ke­nil­worth, NJ-based phar­ma will now be tak­ing an­oth­er lap.

The FDA is de­lay­ing its de­ci­sion on Mer­ck’s gefapix­ant by at least a few months to “pro­vide time for a full re­view of the sub­mis­sion,” the com­pa­ny re­vealed in an SEC fil­ing. The agency, which orig­i­nal­ly set a PDU­FA date for Dec. 21, now ex­pects to make a de­ci­sion by March 21.

Gefapix­ant is one of a few P2X3 re­cep­tor an­tag­o­nists com­pet­ing in the re­frac­to­ry chron­ic cough set­ting, in­clud­ing can­di­dates from Bay­er and Sh­iono­gi. But af­ter Mer­ck’s chief ri­val Bel­lus flopped in a Phase II tri­al last sum­mer, it could be any­one’s game.

For gefapix­ant, the FDA is bas­ing its de­ci­sion on some mixed da­ta from two Phase III tri­als dubbed COUGH-1 and COUGH-2. Re­searchers linked the 45 mg dose to an 18.5% es­ti­mat­ed rel­a­tive risk re­duc­tion in 24-hour cough fre­quen­cy in COUGH-1, meet­ing the pri­ma­ry end­point (p=0.041). In COUGH-2, the same dose led to a 14.6% rel­a­tive risk re­duc­tion (p=0.031). The 15 mg dose, how­ev­er, failed in both tri­als.

Gefapix­ant missed a sec­ondary end­point of awake coughs per hour in COUGH-1, but the high­er dose reached sta­tis­ti­cal sig­nif­i­cance in COUGH-2. In­ves­ti­ga­tors al­so flagged high dropout rates due to ad­verse events, in­clud­ing taste-re­lat­ed side ef­fects, which were ex­pe­ri­enced by more than half of pa­tients giv­en the high­er dose in both tri­als, com­pared to un­der 10% of pa­tients in the place­bo arms.

Bel­lus’ pitch cen­ters on a more se­lec­tive ap­proach that avoids taste-al­ter­ing side ef­fects — but in a mid-stage study, all four dos­es of BLU-5937 fell short of the mark for place­bo-ad­just­ed re­duc­tions in cough­ing. In a Phase IIb study, the com­pa­ny’s en­rolling pa­tients with a base­line awake cough fre­quen­cy of ≥25 awake coughs per hour, where da­ta sug­gest the drug will have a bet­ter chance.

Bay­er’s eli­apix­ant met the pri­ma­ry end­point in a Phase IIb study ear­li­er this month, sig­nif­i­cant­ly im­prov­ing 24-hour cough fre­quen­cy (though the com­pa­ny has yet to re­lease hard da­ta). Sh­iono­gi’s sivopix­ant is in an on­go­ing Phase II study, ac­cord­ing to its web­site.

Mer­ck’s Roy Baynes has big plans for gefapix­ant as a po­ten­tial “pipeline in a prod­uct.” Af­ter buy­ing Af­fer­ent Phar­ma and its P2X3 plat­form for $500 mil­lion up­front in 2016, the com­pa­ny plot­ted a whole range of pro­grams in en­dome­tri­al-re­lat­ed pain, sleep ap­nea and oth­er sen­so­ry re­lat­ed func­tions.

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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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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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.

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.

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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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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Gilead says a net­work of sup­pli­ers and dis­trib­u­tors sold tens of thou­sands of fake ver­sions of its HIV meds

Gilead has accused a network of unauthorized drug suppliers and distributors of selling counterfeit versions of its HIV meds, some of which ended up in US pharmacies, according to court documents unsealed Tuesday.

Over the last two years, Gilead says the distributor defendants sold 85,246 bottles of Gilead meds (including its HIV meds Biktarvy and Descovy) with counterfeit documentation — some of which had tampered bottles, or contained an entirely different drug.