In the hunt for a megablock­buster, Cel­gene plans FDA fil­ing in wake of PhI­II win for ozan­i­mod in MS

When Cel­gene bought out Re­cep­tos and its au­toim­mune drug ozan­i­mod back in 2015 for $7.2 bil­lion in cash, the big biotech bull­ish­ly fore­cast their drug would be worth $4 bil­lion to $6 bil­lion in peak sales. To­day, the ex­ec­u­tive crew start­ed to make good on that pro­jec­tion with a pos­i­tive read­out on the top-line da­ta from their Phase III mul­ti­ple scle­ro­sis study.

The com­pa­ny says it’s on track to file for an ap­proval of the S1P1 re­cep­tor an­tag­o­nist this year.

In­ves­ti­ga­tors weren’t hand­ing out any hard da­ta to­day. But the com­pa­ny says that ozan­i­mod de­liv­ered “sta­tis­ti­cal­ly sig­nif­i­cant and clin­i­cal­ly mean­ing­ful im­prove­ments com­pared to Avonex for the pri­ma­ry end­point of ARR (the an­nu­al­ized re­lapse rate) and the mea­sured sec­ondary end­points of the num­ber of gadolin­i­um-en­hanc­ing MRI le­sions and the num­ber of new or en­larg­ing T2 MRI le­sions at month 12.”

A sec­ond Phase III study in MS will read out in Q2.

This is a tough mar­ket, though. To get any­where close to $6 bil­lion, ef­fi­ca­cy alone won’t cut it. Cel­gene will al­so have to prove a sub­stan­tial safe­ty ad­van­tage with their drug.

Ge­of­frey Porges, Leerink

Just a few days ago Ge­of­frey Porges at Leerink out­lined the strat­e­gy for ozan­i­mod.

Re­sults from the two Ozan­i­mod phase III tri­als in mul­ti­ple scle­ro­sis are due in the first half of this year, with phase III ul­cer­a­tive col­i­tis da­ta ex­pect­ed in the first half of 2018. CELG al­ways as­sumed ozan­i­mod would get same class la­bel­ing match­ing oth­er S1P1 in­hibitors such as Gilenya, but al­so an­tic­i­pate that the phase III safe­ty da­ta would be in the la­bel so that CELG could dis­cuss the po­ten­tial dif­fer­ences with physi­cians and pay­ers. CELG stat­ed the com­pa­ny needs to see “re­al­ly good ef­fi­ca­cy” and a sim­i­lar lack of car­dio and liv­er tox­i­c­i­ty as shown in the phase II tri­al. About 15% of pa­tients dis­con­tin­ue Gilenya due to these tox­i­c­i­ty is­sues. CELG stat­ed that pric­ing will be low­er in UC when the drug is launched in that in­di­ca­tion, and the com­pa­ny plans to use dis­counts by in­di­ca­tion or oth­er meth­ods to match the ex­ist­ing pric­ing in the MS and IBD in­di­ca­tions (at a list price sim­i­lar to the ex­ist­ing $90,000 Gilenya price).

The com­pa­ny said to­day that the safe­ty pro­file of the drug is in line with their Phase II re­sults. And they sound­ed pumped about the prospects of their in­flam­ma­tion and im­munol­o­gy pipeline.

Scott Smith, Cel­gene

Jef­feries’ Bri­an Abra­hams gave the com­pa­ny a quick thumbs up, not­ing that there’s a long way to go be­fore this drug lives up to ex­pec­ta­tions.

We cur­rent­ly mod­el out-year MS sales of ozan­i­mod of ~$1B, giv­en the po­ten­tial Gilenya gener­i­ciza­tion, in­creas­ing com­pe­ti­tion, and grow­ing pric­ing pres­sure in the MS space. While it is not clear whether CELG would de­tail the agent on their own, the com­pa­ny has re­cent­ly shown more open­ness to us­ing ozan­i­mod as a cor­ner­stone to build out a broad­er neu­rol­o­gy com­mer­cial/de­vel­op­ment plat­form. In IBD, we as­sume peak sales ap­proach­ing ~$3.5B in the out-years, and while key ph.III UC da­ta is not ex­pect­ed un­til 2018, we could see some ini­tial Crohn’s dis­ease da­ta that could help clar­i­fy its pro­file and ex­pand­ed IBD po­ten­tial.

“Peo­ple liv­ing with mul­ti­ple scle­ro­sis need ad­di­tion­al ther­a­pies and we are pleased that oral ozan­i­mod showed mean­ing­ful im­prove­ments across pri­ma­ry and mea­sured sec­ondary end­points in this study,” said Scott Smith, pres­i­dent of Cel­gene In­flam­ma­tion and Im­munol­o­gy. “We look for­ward to da­ta from the con­fir­ma­to­ry phase III RA­DI­ANCE tri­al in the sec­ond quar­ter as we ad­vance to­ward planned reg­u­la­to­ry sub­mis­sions by year-end.”

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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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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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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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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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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