Pfiz­er says its JAK drug topped Dupix­ent in a head-to-head eczema test — but you'll have to wait on the da­ta

Just a few hours af­ter Sanofi and Re­gen­eron un­veiled a new slate of da­ta for Dupix­ent in chil­dren with eczema, Pfiz­er re­leased its own re­sults for a JAK chal­lenger. And they come from the first such tri­al show­ing a di­rect head-to-head com­par­i­son be­tween the two.

The New York-based drug gi­ant un­corked topline da­ta from a Phase III study pit­ting its abroc­i­tinib against Dupix­ent, say­ing the ex­per­i­men­tal drug notched su­pe­ri­or­i­ty over the block­buster in mod­er­ate to se­vere atopic der­mati­tis. Abroc­i­tinib met both pri­ma­ry end­points, Pfiz­er said, with a high­er pro­por­tion of pa­tients achiev­ing at least a four-point im­prove­ment over base­line in an itch­i­ness scale and at least 90% im­prove­ment on an eczema in­dex.

Michael Cor­bo

“The re­sults from our first for­mal head-to-head tri­al for abroc­i­tinib il­lus­trate its po­ten­tial for mean­ing­ful symp­tom re­lief for pa­tients,” said Pfiz­er in­flam­ma­tion and im­munol­o­gy chief Michael Cor­bo in a state­ment. “We’re pleased that the study find­ings show the po­ten­tial im­pact abroc­i­tinib could have to help peo­ple liv­ing with mod­er­ate to se­vere atopic der­mati­tis in re­duc­ing their itch sig­nif­i­cant­ly and in achiev­ing near com­plete skin clear­ance.”

Pfiz­er did not re­lease any p-val­ues in the up­date, and added the com­pa­ny will share the da­ta with the FDA “at the ap­pro­pri­ate time.”

Pfiz­er has been re­leas­ing da­ta for abroc­i­tinib, its next-gen fol­low-up on Xel­janz, in a steady flow over the past few years, po­si­tion­ing the pro­gram as a com­peti­tor to Re­gen­eron and Sanofi’s block­buster. Re­searchers have com­plet­ed at least five Phase III stud­ies eval­u­at­ing abroc­i­tinib, com­par­ing the can­di­date on var­i­ous mea­sures against place­bo, such as low­er­ing the rate of flare-ups and com­mon eczema scales.

But Mon­day’s re­sults mark the first time Pfiz­er has giv­en a peek at di­rect head-to-head, piv­otal re­sults be­tween its pro­gram and Dupix­ent, though the two have been mea­sured in ex­plorato­ry end­points in pre­vi­ous stud­ies.

In the study, pa­tients were ran­dom­ized to re­ceive ei­ther 200 mg of oral abroc­i­tinib once a day, or a 300 mg in­jec­tion of Dupix­ent every oth­er week af­ter a 600 mg in­duc­tion dose. Re­searchers re­port­ed for abroc­i­tinib at least a 4-point im­prove­ment in the sever­i­ty of Peak Pru­ri­tus Nu­mer­i­cal Rat­ing Scale (PP-NRS4) from base­line at week 2 and at least a 90% im­prove­ment in the Eczema Area and Sever­i­ty In­dex (EASI)-90 from base­line at week 4.

Re­gard­ing safe­ty, al­ways un­der the spot­light when it comes to the JAK class, Pfiz­er said a larg­er per­cent­age of pa­tients tak­ing abroc­i­tinib saw side ef­fects com­pared to Dupix­ent, but not­ed se­ri­ous and se­vere side ef­fect rates were sim­i­lar in both arms. Two deaths oc­curred in the abroc­i­tinib arm but were deemed un­re­lat­ed to treat­ment — one pa­tient died due to Covid-19, and an­oth­er due to an in­tracra­nial he­m­or­rhage and car­diores­pi­ra­to­ry ar­rest.

The pub­lic will have to wait for ex­act safe­ty fig­ures, but such con­cerns for abroc­i­tinib and oth­er oral JAK in­hibitors are noth­ing new. Pre­vi­ous stud­ies for abroc­i­tinib have shown platelet counts drop­ping 26% for the 200 mg dose com­pared with es­sen­tial­ly no re­duc­tion on place­bo, though they even­tu­al­ly re­turned to nor­mal. Some an­a­lysts have spec­u­lat­ed the drug — or any oth­er JAK, for that mat­ter — may nev­er be con­sid­ered safe enough to tru­ly chal­lenge Dupix­ent on the mar­ket.

Reg­u­la­tors have not weighed in much, but have con­tin­u­al­ly pushed back the PDU­FA dates for mul­ti­ple JAK drugs in eczema, in­clud­ing abroc­i­tinib, Eli Lil­ly’s Olu­mi­ant and Ab­b­Vie’s Rin­voq. Olu­mi­ant and Rin­voq both sport black box warn­ings af­ter win­ning ap­provals for rheuma­toid arthri­tis. Pfiz­er has been down this road be­fore as well with an­oth­er JAK in­hibitor in Xel­janz, which reg­u­la­tors said ne­ces­si­tat­ed a warn­ing back in 2019.

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.

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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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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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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