In a PhI­II show­down with Spark, uniQure switch­es out its lead gene ther­a­py for he­mo­phil­ia B

Late last year, the strug­gling gene ther­a­py biotech uniQure $QURE did some painful cost cut­ting, drop­ping pro­grams, ax­ing staff and tai­lor­ing the pipeline to con­cen­trate on a he­mo­phil­ia B pro­gram for AMT-060, which they said could be hus­tled through a piv­otal pro­gram and in­to the mar­ket, rac­ing with a ri­val ther­a­py from in­dus­try leader Spark Ther­a­peu­tics.

Steven Pipe

This morn­ing, though, uniQure ex­e­cut­ed a quick switch on its lead ef­fort. AMT-060, which had been des­ig­nat­ed as a break­through drug at the FDA, has been re­placed by AMT-061. And the ex­ecs at uniQure say that both the FDA and the EMA have es­sen­tial­ly de­cid­ed to keep this new drug in their VIP drug pro­gram and on the fast track to a reg­is­tra­tion tri­al.

In­vestors loved it. UniQure’s stock shot up more than 60% af­ter the news hit.

The way uniQure makes this sound, re­searchers tweaked their orig­i­nal ther­a­py to come up with some­thing bet­ter. In their state­ment, the biotech says that AMT-060 and AMT-061 are iden­ti­cal ex­cept for “two nu­cleotide sub­sti­tu­tions in the cod­ing se­quence for FIX.”

The gene vari­ant, re­ferred to as FIX-Pad­ua, ex­press­es a pro­tein with a sin­gle amino acid sub­sti­tu­tion that has been re­port­ed in mul­ti­ple pre­clin­i­cal and non­clin­i­cal stud­ies to pro­vide an ap­prox­i­mate 8- to 9-fold in­crease in FIX ac­tiv­i­ty com­pared to the wild-type FIX pro­tein. All oth­er crit­i­cal qual­i­ty at­trib­ut­es of AMT-061 are ex­pect­ed to be com­pa­ra­ble to those of AMT-060, as AMT-061 uti­lizes the same AAV5 cap­sid and pro­pri­etary in­sect cell-based man­u­fac­tur­ing plat­form.

They al­so want to style this new AMT-061 as a much, much bet­ter ther­a­py.

Steven Pipe, pro­fes­sor of pe­di­atrics and pathol­o­gy and pe­di­atric med­ical di­rec­tor of the he­mo­phil­ia and co­ag­u­la­tion dis­or­ders pro­gram at the Uni­ver­si­ty of Michi­gan, had this to say:

“Based on the da­ta gen­er­at­ed to date, AMT-061 may be the first gene ther­a­py to pro­vide durable, cu­ra­tive ben­e­fits to near­ly all pa­tients with he­mo­phil­ia B, with­out the com­pli­ca­tions as­so­ci­at­ed with cap­sid-re­lat­ed im­mune re­spons­es.  I very much look for­ward to serv­ing as an in­ves­ti­ga­tor in this ex­cit­ing Phase III pro­gram.”

Once a leader in gene ther­a­py, uniQure had to drop Gly­bera — ap­proved in Eu­rope but nev­er pitched in the US — af­ter it was re­port­ed­ly used just one time. Now Spark ap­pears to be in the lead af­ter an FDA pan­el en­dorsed its gene ther­a­py for a rare eye dis­ease. And one-time play­er Di­men­sion Ther­a­peu­tics was forced out of he­mo­phil­ia B by weak re­sults, with Ul­tragenyx pick­ing up the rest of the pipeline in a buy­out.

The race goes on.

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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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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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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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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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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