Tedros Adhanom Ghebreyesus (Denis Balibouse/Pool Photo via AP Images)

WHO rec­om­mends against the use of con­va­les­cent plas­ma for Covid-19

The World Health Or­ga­ni­za­tion said late to­day that it’s not rec­om­mend­ing the use of con­va­les­cent plas­ma as a treat­ment for Covid-19 for mild or se­vere cas­es, but some US ex­perts dis­agree with the rec­om­men­da­tions and say there are pa­tients who can ben­e­fit from the plas­ma of those who’ve re­cov­ered from Covid-19.

The rec­om­men­da­tion is in­formed by a re­view of 16 RCTs and a “meta-analy­sis on an­ti­bod­ies and cel­lu­lar ther­a­pies for covid-19,” the WHO said, adding in a state­ment:

De­spite its ini­tial promise, cur­rent ev­i­dence shows that it [con­va­les­cent plas­ma] does not im­prove sur­vival nor re­duce the need for me­chan­i­cal ven­ti­la­tion, and it is cost­ly and time-con­sum­ing to ad­min­is­ter. As such, the WHO makes a strong rec­om­men­da­tion against the use of con­va­les­cent plas­ma in pa­tients with non-se­vere ill­ness, and a rec­om­men­da­tion against its use in pa­tients with se­vere and crit­i­cal ill­ness, ex­cept in the con­text of a ran­domised con­trolled tri­al (RCT).

The WHO wrote in the BMJ that, “Most im­por­tant­ly, giv­en there was no ben­e­fit demon­strat­ed in any of the crit­i­cal or im­por­tant out­comes for non-se­vere covid-19, the GDG [Guide­line De­vel­op­ment Group] did not see any jus­ti­fi­ca­tion for the re­sources (in­clud­ing time and cost) that would be as­so­ci­at­ed with ad­min­is­tra­tion of con­va­les­cent plas­ma.”

The an­nounce­ment builds on re­cent­ly pub­lished da­ta show­ing that while con­va­les­cent plas­ma has proven to be gen­er­al­ly safe, it al­so failed to show signs of ef­fi­ca­cy in some large RCTs of out­pa­tients, in­clud­ing on mor­tal­i­ty in a UK tri­al of those hos­pi­tal­ized with Covid, pub­lished in The Lancet in May, and an­oth­er for out­pa­tients in Au­gust in the New Eng­land Jour­nal of Med­i­cine.

In the re­sults pub­lished in the NE­JM, the NIH-fund­ed tri­al en­rolled more than 500 pa­tients, ran­dom­ized to re­ceive ei­ther plas­ma or place­bo with­in one week af­ter the on­set of symp­toms. Covid-19 pro­gres­sion oc­curred in 77 pa­tients (30%) in the con­va­les­cent plas­ma group and in 81 pa­tients (31.9%) in the place­bo group. Five pa­tients in the plas­ma group and one pa­tient in the place­bo group died, and the tri­al was stopped ear­ly in Feb­ru­ary due to lack of ef­fi­ca­cy.

But ex­perts still think there may be times when con­va­les­cent plas­ma could help peo­ple with Covid-19, ei­ther when it’s de­tect­ed ear­ly enough and high enough titers can be used (as CBER di­rec­tor Pe­ter Marks has said) or for those whose im­mune sys­tems may be de­fi­cient in some way.

“Based on avail­able da­ta I do not agree with this con­clu­sion” from the WHO, Shmuel Shoham, as­so­ciate pro­fes­sor of med­i­cine at Johns Hop­kins Uni­ver­si­ty, told End­points News. “When used at the right time and with high enough titers, COVID-19 Con­va­les­cent Plas­ma (CCP) is ef­fec­tive and gen­er­al­ly safe. The wide­spread avail­abil­i­ty of CCP makes it an op­tion in places where mon­o­clon­al an­ti­bod­ies are not read­i­ly avail­able. There is ad­di­tion­al da­ta that will soon be avail­able from the Johns Hop­kins out­pa­tient stud­ies.”

The FDA still main­tains an EUA for con­va­les­cent plas­ma, which was nar­rowed last Feb­ru­ary to on­ly high titer units and for hos­pi­tal­ized pa­tients who are in the ear­ly stages of the dis­ease. It re­mains to be seen if the WHO’s new rec­om­men­da­tion will change the EUA.

An FDA spokesper­son told End­points that it’s aware of but not com­ment­ing on the WHO’s an­nounce­ment, and the FDA EUA for con­va­les­cent plas­ma re­mains in ef­fect at this time. The EUA was reis­sued on March 9, 2021 and amend­ed in June. The FDA does not col­lect da­ta on how many peo­ple have been treat­ed with con­va­les­cent plas­ma un­der the EUA, and about 70,000 peo­ple ac­cessed con­va­les­cent plas­ma un­der an ex­pand­ed ac­cess pro­gram at the Mayo Clin­ic that the FDA helped to es­tab­lish.

Jeff Hen­der­son, as­so­ciate pro­fes­sor of med­i­cine at Wash­ing­ton Uni­ver­si­ty School of Med­i­cine in St. Louis, told End­points, “Much has been learned about COVID-19 patho­gen­e­sis in the past year and a half. Rel­e­vant to ther­a­peu­tics, we have learned that SARS-CoV-2 patho­gen­e­sis pro­ceeds through an ear­ly phase of vi­ral repli­ca­tion to a lat­er phase of in­flam­ma­tion-as­so­ci­at­ed tis­sue dam­age. Stud­ies that take this in­to ac­count have de­tect­ed ef­fi­ca­cy sig­nals when high titer COVID-19 con­va­les­cent plas­ma is ad­min­is­tered ear­ly in dis­ease to pa­tients with mild to mod­er­ate COVID-19.”

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.

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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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.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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Albert Bourla, Pfizer CEO (Evan Vucci, AP Images)

Covid-19 roundup: Pfiz­er ex­pands in­to France; Omi­cron-spe­cif­ic ver­sion of Mod­er­na's boost­er com­ing soon 

As the hype surrounding Pfizer’s antiviral Covid-19 pill swirls, the pharma announced that it will build a production facility in France to make the drug as a part of a five-year investment.

Pfizer will team up with Novasep to install equipment and initiate tech transfer and on-site development at Novasep’s Mourenx facility. The move is a part of a $594 million investment in France.

“We are of course proud to contribute to the manufacturing of this medicine which has shown in clinical trials to have a positive impact on hospitalization among at-risk Covid-19 patients,” Novasep’s CEO Michel Spagnol said in a statement. “This contract also validates our investment strategy for several years and our focus on small molecules.”