Tedros Adhanom Ghebreyesus, WHO Director-General (Fabrice Coffrini/AFP via Getty Images)

UK in­ves­ti­ga­tors say a drug re­duced Covid-19 deaths for the first time. The world pon­ders what to do next

In the hours af­ter UK in­ves­ti­ga­tors said that, for the first time, a drug had been shown to help pre­vent deaths in Covid-19 pa­tients, a world of doc­tors, pub­lic health re­searchers and reg­u­la­tors were left try­ing to fig­ure out what it meant and how to re­spond.

Britain’s NHS act­ed first, au­tho­riz­ing the drug, a gener­ic steroid called dex­am­etha­sone, with­in hours of the study an­nounce­ment. Prais­ing the study’s in­ves­ti­ga­tors, the agency said the drug would be­come the new stan­dard of care and avail­able through­out the coun­try.

Matt Han­cock UK Par­lia­ment

“From to­day, the stan­dard of treat­ment for Covid-19 will in­clude dex­am­etha­sone, help­ing save thou­sands of lives while we deal with this ter­ri­ble virus,” health sec­re­tary Matt Han­cock said in a state­ment.

Else­where, though, the re­sponse was slow­er. Even as many doc­tors em­braced the re­sults as the first ma­jor break­through for se­vere Covid-19 pa­tients — and ar­guably the biggest med­ical break­through since the start of the pan­dem­ic — oth­ers preached cau­tion, at least un­til the full da­ta were re­leased. Af­ter scores of com­pa­nies re­leased da­ta by press re­lease rather than in pub­li­ca­tions, and ear­li­er this month a pair of hy­drox­y­chloro­quine stud­ies were re­tract­ed from pres­ti­gious jour­nals, they were wary of claim­ing suc­cess too soon.

Har­lan Krumholz

“This is a high­ly rep­utable group — but still we need more in­for­ma­tion about the study,” Har­lan Krumholz, a car­di­ol­o­gist and pro­fes­sor of med­i­cine at the Yale School of Med­i­cine, said in an email.

WHO in­spec­tor gen­er­al Dr. Tedros Ad­hanom Ghe­breye­sus called the study “great news” and said they would move to re­vise treat­ment guide­lines. They are wait­ing, though, to re­ceive full de­tails from the study and will con­duct a meta-analy­sis “to in­crease our un­der­stand­ing of the in­ter­ven­tion.”

The FDA wouldn’t com­ment on whether they would au­tho­rize dex­am­etha­sone. A spokesper­son for the In­fec­tious Dis­eases So­ci­ety of Amer­i­ca said they would in­clude a “dis­cus­sion” of the drug but not a rec­om­men­da­tion in their next guide­lines on April. “That will like­ly change as more re­search builds on their ef­fec­tive­ness,” they said.

The 6,000-per­son RE­COV­ERY study, run by in­ves­ti­ga­tors at the Uni­ver­si­ty of Ox­ford, found that the cheap and wide­ly-avail­able steroid low­ered the risk of death for pa­tients on ven­ti­la­tors by about a third and for se­vere­ly ill pa­tients who on­ly re­quired oxy­gen by about a fifth. Af­ter the NIH remde­sivir tri­al, it was the first ran­dom­ized con­trolled study to show a drug could be ef­fec­tive and it was the first such tri­al to show a drug could re­duce mor­tal­i­ty.

“These UK re­cov­ery tri­al da­ta are the re­al deal,” David Boul­ware, an in­fec­tious dis­ease spe­cial­ist at the Uni­ver­si­ty of Min­neso­ta who led one of the first ran­dom­ized hy­drox­y­chloro­quine stud­ies, told End­points News in an email.“This is the first ther­a­py that has con­clu­sive da­ta demon­strat­ing ben­e­fit in those crit­i­cal­ly ill ICU pa­tients.”

David Boul­ware

Boul­ware said the da­ta made it “pret­ty clear” who should get the drug, echo­ing com­ments yes­ter­day from lead in­ves­ti­ga­tor Pe­ter Horn­by that dex­am­etha­sone should be­come the new stan­dard of care for ICU pa­tients.

Many doc­tors had al­ready been giv­ing pa­tients dex­am­etha­sone off-la­bel. Now it’s like­ly that even more will, said Ali Khan, the for­mer di­rec­tor of the CDC’s Of­fice of Pub­lic Health Pre­pared­ness, “giv­en we were oth­er us­ing snake oil.”

Point­ing to the mor­tal­i­ty da­ta, Memo­r­i­al Sloan Ket­ter­ing’s Pe­ter Bach said on Twit­ter that for oxy­genat­ed pa­tients, dex­am­etha­sone might be a bet­ter op­tion than remde­sivir. The NIH’s remde­sivir study, re­sults from which were an­nounced at the end of April and pub­lished last month, showed im­proved time to re­cov­ery in some pa­tients. That tri­al did not, how­ev­er, prove the an­tivi­ral could boost sur­vival for any­one, nor ben­e­fit ICU pa­tients at all.

On Twit­ter, doc­tor, pub­lic health re­searcher, and writer At­ul Gawande crit­i­cized the in­ves­ti­ga­tors. In light of re­cent re­trac­tions – in­clud­ing a pair of hy­drox­y­chloro­quine stud­ies pulled from The Lancet and the New Eng­land Jour­nal of Med­i­cine – he ar­gued “it is un­ac­cept­able to tout study re­sults by press re­lease with­out re­leas­ing the pa­per.”

The re­trac­tions, though, had to do with faulty da­ta from elec­tron­ic med­ical records, rather than a ran­dom­ized con­trolled study like the dex­am­etha­sone tri­al.

Ali Khan

”Ques­tions about COVID-19 stud­ies us­ing elec­tron­ic da­ta are ir­rel­e­vant,” Khan, now a pro­fes­sor at the Uni­ver­si­ty of Ne­bras­ka Med­ical School, said in an email. He not­ed that the FDA au­tho­rized remde­sivir 4 days af­ter the topline re­sults were an­nounced — and near­ly a month be­fore the full da­ta were pub­lished.

The re­sults will al­so have im­pli­ca­tions for com­pa­nies run­ning tri­als on oth­er Covid-19 drugs. A spokesper­son for Re­gen­eron told STAT yes­ter­day that the tri­als for their Covid-19 an­ti­bod­ies have pro­to­cols that al­low them to change the stan­dard of care arm if new ev­i­dence aris­es. A spokesper­son for Mer­ck, which is test­ing an an­tivi­ral in hu­mans, said “it is too ear­ly to spec­u­late” on how the study could af­fect their tri­als.

“We look for­ward to re­view­ing the full re­sults of the U.K. RE­COV­ERY tri­al when they be­come avail­able,” they said.

Like most drugs, dex­am­etha­sone is not with­out side ef­fects. Jairam Lin­gap­pa, a pro­fes­sor of pub­lic health at the Uni­ver­si­ty of Wash­ing­ton and a CDC of­fi­cial dur­ing the SARS out­break, said that if the study held up through peer re­view, the drug would be help­ful but “wasn’t a fi­nal an­swer.” He not­ed that dex­am­etha­sone has been life-sav­ing for sev­er­al in­flam­ma­to­ry con­di­tions, in­clud­ing bac­te­r­i­al menin­gi­tis, but it can al­so lead to an in­creased risk of in­fec­tion.

Jairam Lin­gap­pa

That makes it, he said, more of a stop­gap while di­rect­ly tar­get­ed drugs, such as cer­tain an­ti­bod­ies and an­tivi­rals, go through de­vel­op­ment.

“Hav­ing some­thing more spe­cif­ic for COVID will like­ly avoid some of those risks,” he wrote in an email. “But cer­tain­ly it pro­vides a help­ful op­tion in the face of dis­as­ter.”

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

Ugur Sahin, BioNTech CEO (Bernd von Jutrczenka/dpa via AP Images)

BioN­Tech is spear­head­ing an mR­NA vac­cine de­vel­op­ment pro­gram for malar­ia, with a tech trans­fer planned for Africa

Flush with the success of its mRNA Covid-19 vaccine, BioNTech is now gearing up for one of the biggest challenges in vaccine development — which comes without potential profit.

The German mRNA pioneer says it plans to work on a jab for malaria, then transfer the tech to the African continent, where it will work with partners on developing the manufacturing ops needed to make this and other vaccines.

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How one start­up fore­told the neu­ro­science re­nais­sance af­ter '50 years of shit­show'

In the past couple of years, something curious has happened: Pharma and VC dollars started gushing into neuroscience research.

Biogen’s controversial new Alzheimer’s drug Aduhelm has been approved on the basis of removing amyloid plaque from the brain, but the new neuro-focused pharma and biotechs have much loftier aims. Significantly curbing or even curing the most notorious disorders would prove the Holy Grail for a complex system that has tied the world’s best drug developers in knots for decades.

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Busi­ness­es and schools can man­date the use of Covid-19 vac­cines un­der EUAs, DOJ says

As public and private companies stare down the reality of the Delta variant, many are now requiring that their employees or students be vaccinated against Covid-19 prior to attending school or to returning or starting a new job. Claims that such mandates are illegal or cannot be used for vaccines under emergency use authorizations have now been dismissed.

Setting the record straight, the Department of Justice on Monday called the mandates legal in a new memo, even when used for people with vaccines that remain subject to EUAs.

Why is On­col­o­gy Drug De­vel­op­ment Re­search Late to the Dig­i­tal Bio­mark­ers Game?

During the recent Annual ASCO Meeting, thousands of cancer researchers and clinicians from across the globe joined together virtually to present and discuss the latest findings and breakthroughs in cancer research and care. There were more than 5000+ scientific abstracts presented during this event, yet only a handful involved the use of motion-tracking wearables to collect digital measures relating to activity, sleep, mobility, functional status, and/or quality of life. Although these results were a bit disappointing, they should come as no surprise to those of us in the wearable technology field.

Bob Bradway, Amgen CEO (Scott Eisen/Bloomberg via Getty Images)

Am­gen bel­lies back up to the M&A ta­ble for an­oth­er biotech buy­out, this time with a $2.5B deal for an an­ti­body play­er fo­cused on PS­MA

Five months after Amgen CEO Bob Bradway stepped up to the M&A table and acquired Five Prime for $1.9 billion, following up with the smaller Rodeo acquisition, he’s gone back in for another biotech buyout.

This time around, Amgen is paying $900 million cash while committing up to $1.6 billion in milestones to bag the privately held Teneobio, an antibody drug developer that has expertise in developing new bispecifics and multispecifics. In addition, Amgen cited Teneobio’s “T-cell engager platform, which expands on Amgen’s existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform.”

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Frank Pallone (Kevin Dietsch/Pool via AP Images)

House com­mit­tee seeks more from FDA on in­spec­tion back­log, when to restart work on for­eign sites

House Energy & Commerce committee leaders are raising fresh questions about the FDA’s ability to conduct foreign manufacturing site inspections and bring down its growing backlog.

“While we understand that the emergence of COVID-19 required the agency to suspend in-person inspection activities temporarily, we remain concerned that more than one year into the pandemic, the strategy for resuming all inspections and addressing the backlog of delayed inspections remains unclear,” E&C chair Frank Pallone (D-NJ) and a group of five other bipartisan leaders of the committee wrote to FDA acting commissioner Janet Woodcock.

Art Levinson (Calico)

Google-backed Cal­i­co dou­bles down on an­ti-ag­ing R&D pact with Ab­b­Vie as part­ners ante up $1B, start to de­tail drug tar­gets

Seven years after striking up a major R&D alliance, AbbVie and Google-backed anti-aging specialist Calico are doubling down on their work with a joint, $1 billion commitment to continuing their work together. And they’re also beginning to offer some details on where this project is taking them in the clinic.

According to their statement, each of the two players is putting up $500 million more to keep the labs humming.

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UP­DAT­ED: Pan­el of neu­ro­science ex­perts lays out the com­pli­ca­tions with us­ing Bio­gen's new Alzheimer's drug

Treatment of early Alzheimer’s patients with Biogen’s new drug Aduhelm should closely resemble how the drug was studied in its pivotal clinical trials, according to new recommendations from a panel of neuroscience experts led by UNLV’s Jeffrey Cummings.

“Those considering aducanumab therapy should understand that the expected benefit is slowing of cognitive and functional decline; improvement of the current clinical state is not anticipated,” they wrote Tuesday in The Journal of Prevention of Alzheimer’s Disease, noting that some of their recommendations are more specific or more restrictive than the information provided in the FDA’s prescribing information.

Covid-19 roundup: Till­man Gern­gross inks deal to bring an­ti­body can­di­date to In­dia; At FDA's re­quest, mR­NA vac­cine mak­ers will ex­pand tri­als for chil­dren ages 5-11

A week after it was reported that India’s Covid-19 death toll could be in the millions, antibody legend Tillman Gerngross has inked a deal to develop Adagio’s lead candidate for the treatment and prevention of the virus in southern Asia.

Adagio is joining hands with Biocon Biologics to manufacture and commercialize a treatment based on ADG20 in India and “select emerging markets,” the companies announced on Monday. Under the agreement, Adagio will provide Biocon with materials and know-how to make the therapy, including data from ongoing Phase II/III trials and (if all goes well) access to its potential EUA package.