UP­DAT­ED — Covid-19 roundup: WHO all but con­firms virus not man-made; Neu­roRx, Re­lief say they don't know if IV treat­ment works

The WHO has been work­ing on trac­ing the ori­gins of the Covid-19 pan­dem­ic in re­cent weeks, send­ing a field team to Wuhan, Chi­na, to in­ves­ti­gate. And Tues­day morn­ing, they all but ruled out the pos­si­bil­i­ty that the virus was man-made.

Re­searchers with the or­ga­ni­za­tion said the nov­el coro­n­avirus stem­ming from the re­sult of a lab ac­ci­dent was “ex­treme­ly un­like­ly,” con­firm­ing what most health ex­perts had said since it first emerged in late 2019. The ev­i­dence con­tin­ues to point to­ward the virus spread­ing from an­i­mals to hu­mans.

“All the work that has been done on the virus and try­ing to iden­ti­fy its ori­gin con­tin­ue to point to­ward a nat­ur­al reser­voir,” lead sci­en­tist Pe­ter Ben Em­barek said at a news con­fer­ence, per a New York Times re­port.

In speak­ing with re­porters, Em­barek swat­ted down the lab ac­ci­dent the­o­ry that had been pro­mot­ed at times by for­mer Pres­i­dent Don­ald Trump’s ad­min­is­tra­tion, among oth­ers. “It was very un­like­ly that any­thing could es­cape from such a place,” he said, not­ing the heavy safe­ty pro­to­cols.

The WHO mis­sion comes af­ter months of crit­i­cism that the or­ga­ni­za­tion has gone out of its way to de­fer to the Chi­nese gov­ern­ment in its as­sess­ments of the pan­dem­ic. Chi­na had been re­luc­tant to al­low the sci­en­tists in­to the coun­try but ul­ti­mate­ly ac­qui­esced last month, let­ting the group of 14 con­duct their in­ves­ti­ga­tion.

The coun­try al­so used Tues­day’s news con­fer­ence to con­tin­ue as­sert­ing that the virus first ap­peared else­where, a the­o­ry that many health ex­perts dis­miss. WHO sci­en­tists have said they will in­ves­ti­gate these claims while al­so call­ing for more re­search in­to an­i­mals sold at a mar­ket in Wuhan where some of the first cas­es were re­port­ed.

Ef­fi­ca­cy for se­vere Covid-19 treat­ment still TBD, Neu­roRx and Re­lief say

Neu­roRx and Re­lief Ther­a­peu­tics have teamed up on de­vel­op­ing in­haled and IV for­mu­la­tions of an ex­per­i­men­tal drug for se­vere Covid-19 cas­es, and on Tues­day re­vealed that the ju­ry is still out on whether or not the IV pro­gram works as in­tend­ed.

The pair said they are still work­ing to de­ter­mine whether or not the can­di­date, dubbed Zye­sa­mi, met the pri­ma­ry end­point of re­cov­ery from res­pi­ra­to­ry fail­ure with­in 28 days in a Phase IIb/III study. Pa­tients are be­ing fol­lowed through 60 days.

The pair al­so re­vealed key sec­ondary end­point da­ta, in­clud­ing that re­searchers did not see dif­fer­ences in sur­vival ben­e­fit af­ter four weeks. Neu­roRx and Re­lief ap­peared to blame that on over­all ICU care im­prov­ing, say­ing in a re­lease “With the im­prove­ment in sur­vival since the start of the pan­dem­ic, dif­fer­ences in sur­vival were not seen at day 28.”

In­vestors in Re­lief were ap­par­ent­ly not pleased, send­ing shares of the Swiss pen­ny stock down more than 30%.

138 pa­tients out of a to­tal of 203 sur­vived in that time­frame, with 91 of those tak­ing Zye­sa­mi and 47 on stan­dard of care. Pa­tients were ran­dom­ized in­to the drug arm at a 2-to-1 ra­tio.

The com­pa­nies at­tempt­ed to high­light a small pos­i­tive in an­oth­er sec­ondary end­point, though, not­ing that pa­tients who were treat­ed with Zye­sa­mi on top of the max­i­mal stan­dard of care ben­e­fit­ed over place­bo. They mea­sured this out­put us­ing time to dis­charge from the hos­pi­tal, say­ing that in six of eight evalu­able cas­es pa­tients saw a three-day me­di­an dif­fer­ence in hos­pi­tal stay.

But by the com­pa­nies’ own ad­mis­sion, that find­ing may not end up mean­ing any­thing.

“The sec­ondary end­point da­ta re­port­ed to­day should not cre­ate an ex­pec­ta­tion that the pri­ma­ry end­point will be met over­all or for any sub­group,” the com­pa­nies said.

End­points News sent out a re­quest for com­ment on the news, and re­ceived this in an emailed re­sponse from CEO Jonathan Javitt:

“The end­point da­ta we re­port­ed are sta­tis­ti­cal­ly-sig­nif­i­cant and clin­i­cal­ly mean­ing­ful to doc­tors, pa­tients, and fam­i­lies. Re­duced hos­pi­tal stay has been a key ba­sis for reg­u­la­to­ry de­ter­mi­na­tions dur­ing the COVID pan­dem­ic and the re­duced hos­pi­tal stay seen in this pop­u­la­tion was shown in a pop­u­la­tion that lacks ef­fec­tive ther­a­pies. These da­ta are there­fore ma­te­r­i­al.”

The can­di­date it­self is a for­mu­la­tion of va­soac­tive in­testi­nal polypep­tide, which is known to be high­ly con­cen­trat­ed in the lungs. Though Tues­day’s re­sults come from the IV ver­sion of the pro­gram, the in­haled for­mu­la is cur­rent­ly in a Phase II/III study.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

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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Covid-19 roundup: HHS may strug­gle to ab­sorb Op­er­a­tion Warp Speed; Eu­rope has no plans for a fourth vac­cine dose

Operation Warp Speed, perhaps the greatest achievement of the former Trump administration, promptly delivered Covid-19 vaccine supplies nationwide when they became available, thanks to collaborations between HHS and the Department of Defense, while helping to fund and aid the manufacture of billions of doses.

But since the Biden administration took over a year ago, acting FDA commissioner Janet Woodcock transitioned out of her role as the therapeutics lead in Warp Speed, which has been converted into a new operation without the fancy name (now known as the “HHS-DOD COVID-19 Countermeasures Acceleration Group”), and as of the start of 2022, the Department of Defense is no longer helping HHS on the program.

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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