Bio­gen ex­tends its set­back streak as Japan­ese reg­u­la­tors push back against their con­tro­ver­sial Alzheimer's drug

An­oth­er bad week for Bio­gen and its Tokyo-based part­ners at Ei­sai was ex­tend­ed on Wednes­day with news that a pan­el re­view of their con­tro­ver­sial Alzheimer’s drug ad­u­canum­ab earned a push­back from the health min­istry in Japan.

Ac­cord­ing to overnight news re­ports, their pan­el con­clud­ed that in­con­sis­tent Phase III da­ta and lack of clin­i­cal sig­nif­i­cance in re­duc­ing amy­loid plaque in pa­tients made it dif­fi­cult to de­ter­mine if the ther­a­py worked, but of­fered to re­view it again once the 2 part­ners lined up more da­ta.

That lat­est push­back comes just days af­ter Bio­gen and Ei­sai were forced to dig a de­fen­sive perime­ter around the for­mal Eu­ro­pean reg­u­la­to­ry de­ci­sion against an ap­proval and right on the heels of Bio­gen’s de­ci­sion to slash the US price and be­gin a com­pa­ny re­or­ga­ni­za­tion as sales stag­nate in the face of deeply em­bed­ded re­sis­tance to the drug — which of­fered one of the most con­tro­ver­sial ap­provals in FDA his­to­ry.

Bio­gen says it’s not giv­ing up on Japan. In a state­ment sent to End­points News, a spokesper­son not­ed:

The com­pa­nies will con­tin­ue to ac­tive­ly en­gage with the Phar­ma­ceu­ti­cals and Med­ical De­vices Agency (PM­DA) in Japan to agree on ad­di­tion­al da­ta re­quire­ments. Bio­gen and Ei­sai re­main com­mit­ted to bring­ing ad­u­canum­ab to pa­tients in Japan ex­pe­di­tious­ly.

Japan was seen as a pos­si­ble op­por­tu­ni­ty to stop some of the bleed­ing over the dis­as­trous roll­out, with Ei­sai deeply en­trenched in the coun­try and look­ing to mar­ket what it and its part­ners in­sist is the first dis­ease-mod­i­fy­ing drug for Alzheimer’s. Ei­sai spear­head­ed the reg­u­la­to­ry ef­fort in Japan and stood to earn the li­on’s share of the mon­ey from the big Asian mar­ket.

Ex­perts, though, have shak­en their heads in uni­son over a mud­dle of con­flict­ing da­ta, per­plexed that the FDA would of­fer an ac­cel­er­at­ed ap­proval based on the sus­pect the­o­ry that amy­loid re­duc­tion would like­ly help pa­tients fight back against the steady drain of their mem­o­ries.

Those ex­perts show no sign of go­ing away, as we al­so saw this week with a line­up of re­searchers in the field who signed a pe­ti­tion de­mand­ing the FDA pro­vide an ac­cel­er­at­ed with­draw­al of the drug from the US mar­ket.

As of to­day, the FDA re­mains the sole pre­mier drug agency in the world that thinks the drug should be on the mar­ket, based on what we know so far.

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.

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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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.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

An­oth­er day, an­oth­er xeno­trans­plant, as Unit­ed Ther­a­peu­tics looks to beat com­peti­tors to sci-fi-es­que break­through

Xenotransplantation is having a moment.

Last October, a team from NYU successfully transplanted a kidney from a pig into a brain-dead patient, although observers cast doubt on the importance of the experiment. Then, earlier this month, surgeons at the University of Maryland transplanted a pig heart into a dying human, who appears to still be stable.

Now, another group is planting a flag in the xenotransplantation field. Surgeons at the University of Alabama at Birmingham said Thursday they have achieved the first kidney transplant from a pig to a brain-dead patient, publishing their peer-reviewed findings online. The team, aiming to differentiate itself from the others through the genetic modifications used, is hoping there’s now enough research to soon begin clinical xenotransplantation studies.

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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