A spot­light schiz­o­phre­nia drug in Neu­ro­crine's $2B Take­da deal flunks its first ma­jor test. But it's not giv­ing up yet

When Take­da spun out a pipeline of ex­per­i­men­tal psy­chi­a­try drugs to Neu­ro­crine in a $2 bil­lion deal amid a post-merg­er shake­out, R&D chief Andy Plump de­scribed the ther­a­pies as “very in­ter­est­ing but still dif­fi­cult.”

On Tues­day, we got some idea of how dif­fi­cult.

Eiry Roberts

San Diego-based Neu­ro­crine re­vealed that one of the three spot­light clin­i­cal pro­grams they’d ac­quired failed the pri­ma­ry end­point in a Phase II tri­al for schiz­o­phre­nia, reg­is­ter­ing a neg­a­tive out­come on the change from base­line in the pos­i­tive and neg­a­tive syn­drome scale/neg­a­tive symp­tom fac­tor score (PANSS NS­FS).

CMO Eiry Roberts not­ed the IN­TER­ACT study, which en­rolled 256 pa­tients and test­ed three dos­ing lev­els of lu­vadax­i­s­tat in a place­bo-con­trolled set­ting, was “well-de­signed and ex­e­cut­ed” — leav­ing lit­tle room to ma­neu­ver in that end­point. The PANSS score is de­signed to as­sess sever­i­ty of schiz­o­phre­nia symp­toms.

From RBC an­a­lyst Bri­an Abra­hams:

Our sense is that the miss on the pri­ma­ry end­point, the PANSS neg­a­tive score, was like­ly due to a true lack of ef­fi­ca­cy, rather than any con­duct is­sues such as base­line im­bal­ances, glob­al site vari­abil­i­ty or high place­bo ef­fect, though the com­pa­ny has not yet com­plet­ed full analy­sis of PK char­ac­ter­i­za­tion (re­call there is a mod­est food ef­fect). The com­pa­ny is not re­port­ing whether there were any no­table trends or dose de­pen­dent sig­nals, sug­gest­ing there like­ly were none.

There is, though, still a sil­ver lin­ing. The drug — al­so known as TAK-831 — met the sec­ond end­points as­sess­ing cog­ni­tive per­for­mance, and the side ef­fects ap­peared con­sis­tent with pre­vi­ous stud­ies.

All of that backs fur­ther clin­i­cal work with the help of Take­da, Roberts added.

Neu­ro­crine had put down $120 mil­lion up­front to get its hands on a pack­age of three clin­i­cal-stage drugs, plus four more pre­clin­i­cal ther­a­pies. Take­da is then in line for $495 mil­lion in de­vel­op­ment mile­stones plus $1.4 bil­lion in com­mer­cial goal cash as well as roy­al­ties. Or it can trade in some of those mile­stones in fa­vor of a 50:50 prof­it share — should it choose to opt-in.

The deal marked one of the last steps of a ma­jor R&D re­org at Take­da, which was look­ing to shed some weight and earn some cash af­ter pay­ing $62 bil­lion to merge with Shire.

And the turn to fo­cus on sec­ondary end­points was an op­tion baked in­to the lu­vadax­i­s­tat pro­gram, ex­ecs told Stifel an­a­lyst Paul Mat­teis.

“(A)t the out­set of this pro­gram, Take­da had been de­bat­ing on whether to de­vel­op in schiz­o­phre­nia neg­a­tive symp­toms or cog­ni­tion, so a sig­nal on the lat­ter does align with some of the orig­i­nal sci­en­tif­ic hy­pothe­ses,” he wrote, adding that they al­so em­pha­sized “cog­ni­tive im­pair­ment in schiz­o­phre­nia is a big un­met need and worth pur­su­ing. That said, there’s al­so a lot of opac­i­ty here and ze­ro da­ta to an­a­lyze, so while the sec­ondary end­point sig­nal seems in­ter­est­ing and may cush­ion the hit to the stock, it will take a full pre­sen­ta­tion/pub­li­ca­tion to re­al­ly un­der­stand the prospects of ‘831.”

Shares in Neu­ro­crine $NBIX end­ed up falling 7.05% to $101.71.

We will have to wait for the da­ta. The com­pa­ny says it’s eval­u­at­ing the re­sults to de­ter­mine the next steps.

Kevin Gor­man, Neu­ro­crine CEO

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.

What lured Hal Bar­ron away?; Top FDA minds on ac­cel­er­at­ed ap­proval re­forms; ‘Dead wrong’ Aduhelm ad blitz; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Nothing can really compete with Hal Barron’s departure from GlaxoSmithKline as the news of the week, but we do have plenty of original reporting and analysis from the Endpoints team in this edition. Enjoy and have a nice weekend.

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Mer­ck wins le­gal bat­tle over in­sur­ance cov­er­age af­ter ran­somware at­tack

Merck has emerged victorious from a years-long legal battle with insurers over the coverage of more than a billion dollars in losses from the malware NotPetya, with a New Jersey Superior Court judge concluding that the responsibility is on insurers to clarify their policies around cyber attacks.

The pharma giant was one of several victims of a global cyber attack back in 2017 that also hit Danish shipping company Maersk, American food company Mondelēz, French construction giant Saint-Gobain and even the systems monitoring the Chernobyl nuclear power stations, Bloomberg reported back in 2019.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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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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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.