Da­ta sug­gest US, UK uni­ver­si­ties fall woe­ful­ly short on re­port­ing clin­i­cal tri­al re­sults

Clin­i­cal tri­al da­ta are used by pa­tients, doc­tors and pol­i­cy­mak­ers to make in­formed choic­es about the ben­e­fits and safe­ty of in­ter­ven­tions — while the meth­ods and re­sults of all tri­als are cru­cial to the pace and di­rec­tion of sci­en­tif­ic progress. How­ev­er, there is a large body of ev­i­dence that sug­gests that com­plet­ed clin­i­cal tri­als are com­mon­ly left un­re­port­ed, and ed­u­ca­tion­al in­sti­tu­tions in the Unit­ed States and the Unit­ed King­dom — ar­guably the two biggest re­gions that breed the bulk of med­ical in­no­va­tion — have emerged as one of the key cul­prits guilty of these vi­o­la­tions.

In the Unit­ed States, Con­gress passed a law in 2007 re­quir­ing tri­al spon­sors — in­clud­ing uni­ver­si­ties — to post the re­sults of cer­tain clin­i­cal tri­als on clin­i­cal­tri­als.gov with­in a year of tri­al com­ple­tion, and a decade lat­er in Jan­u­ary 2017 the rule was fi­nal­ized. Since 2017, 40 lead­ing US uni­ver­si­ties should have post­ed the re­sults of 450 clin­i­cal tri­als — but over a third (31%) of those re­sults are miss­ing, ac­cord­ing to an analy­sis by Uni­ver­si­ties Al­lied for Es­sen­tial Med­i­cines (UAEM) in part­ner­ship with non-prof­it re­search ad­vo­ca­cy group TranspariMED.

The vi­o­la­tors in­clude some of the most ac­tive tri­al spon­sors: For ex­am­ple the MD An­der­son Can­cer Cen­ter, which has on­ly re­port­ed 77% of due tri­als, Mayo Clin­ic (42%), UC San Fran­cis­co (37%), New York Uni­ver­si­ty (21%), and Co­lum­bia Uni­ver­si­ty (17%).

A sum­ma­ry of re­sults by per­cent­age of each uni­ver­si­ty eval­u­at­ed can be seen be­low:

Source: UAEM, TranspariMED

Click on the im­age to see the full-sized ver­sion

Over­all, 140 clin­i­cal tri­als are still miss­ing re­sults and five uni­ver­si­ties are re­spon­si­ble for half of the un­re­port­ed tri­als: Uni­ver­si­ty of Cal­i­for­nia San Fran­cis­co (17 tri­als with­out re­sults), Co­lum­bia (15 tri­als), Mayo Clin­ic (13), MD An­der­son Can­cer Cen­ter (12) and Chica­go (8), ac­cord­ing to the re­port.

These trans­paren­cy vi­o­la­tions are con­cern­ing con­sid­er­ing at least half of the valu­able med­i­cines that ex­ist to­day were orig­i­nal­ly de­vel­oped in uni­ver­si­ty labs with tax­pay­er fund­ing, in­clud­ing al­most all vac­cines, many HIV and tu­ber­cu­lo­sis drugs, and even in­sulin, the re­port not­ed. Be­tween 2010 and 2016, every sin­gle one of the 210 FDA-ap­proved med­i­cines can be traced back to fund­ing from the NIH, ac­cord­ing to a study pub­lished in the of­fi­cial jour­nal of the Na­tion­al Acad­e­my of Sci­ences.

Mean­while, these trans­paren­cy trans­gres­sions are echoed in the UK. Reg­u­la­tions in Eu­rope are sim­i­lar. Any tri­al of of any med­i­c­i­nal prod­uct con­duct­ed since 2004 in an EU coun­try has al­ready been re­quired to reg­is­ter on the Eu­ro­pean Union Clin­i­cal Tri­als Reg­is­ter (EU­C­TR) and since 2012, spon­sors must en­sure that all reg­is­tered tri­als since 2004 dis­close their re­sults to the EMA with­in 12 months of tri­al com­ple­tion. But the de­lays to the EMA’s soft­ware plat­form pushed the fi­nal date for re­sults post­ing by spon­sors to late De­cem­ber 2016.

Ben Goldacre

In a BMJ study pub­lished in 2018 — led by Ben Goldacre, a best-sell­ing au­thor, med­ical doc­tor and re­searcher who fo­cus­es on un­pack­ing the mis­use of sci­ence and sta­tis­tics in his books Bad Sci­ence and Bad Phar­ma — it was found that in Eu­rope, of the 7274 tri­als where re­sults were due, 49.5% re­port­ed re­sults. Tri­als with a com­mer­cial spon­sor (such as a drug de­vel­op­er) were sub­stan­tial­ly more like­ly to post re­sults than those with a non-com­mer­cial spon­sor (68.1% v 11.0%), the analy­sis sug­gest­ed.

Out of his labs at the Uni­ver­si­ty of Ox­ford, Goldacre set up an EU Tri­al­sTrack­er to con­tin­u­ous­ly mon­i­tor the re­port­ing of tri­als. As of 10 Jan­u­ary 2019, Goldacre and his team have iden­ti­fied 8,062 reg­is­tered tri­als that are ‘un­am­bigu­ous­ly’ due to re­port re­sults — but re­sults on just over half  (53.6%) have been post­ed to the reg­istry. The da­ta, which sug­gest­ed that UK uni­ver­si­ties were less re­li­able than drug de­vel­op­ers, sparked the in­ter­est of House of Com­mons Sci­ence and Tech­nol­o­gy Com­mit­tee. UK uni­ver­si­ties could be brought in front of the com­mit­tee if they fail to im­prove their track record, and the com­mit­tee will ask them to ex­plain them­selves in a fol­low-up ev­i­dence ses­sion if im­prove­ments are not made.

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.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

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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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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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