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.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

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New stan­dard of care? FDA hands Pfiz­er, Mer­ck KGaA an OK for Baven­cio in blad­der can­cer

The breakthrough therapy designation Pfizer and Merck KGaA notched for Bavencio in bladder cancer has quickly paved way for a full approval.

The PD-L1 drug is now sanctioned as a first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma, applicable in cases where cancer hasn’t progressed after platinum-containing chemotherapy.

Petros Grivas, the principal investigator of the supporting Phase III JAVELIN Bladder 100, called the approval “one of the most significant advances in the treatment paradigm in this setting in 30 years.”

Covid-19 roundup: Vac­cines will need to beat place­bo by 50% to qual­i­fy for FDA OK; UK tri­al drops Kale­tra

The FDA will set the bar for approving a Covid-19 vaccine at 50% efficacy, the Wall Street Journal reported, meaning any successful candidate will have to reduce the risk of coronavirus disease by at least half compared to placebo.

That requirement is part of guidance that the agency is set to release later today, laying out detailed criteria for vaccine developers — some of whom are eyeing an OK by the end of the year, in line with expectations at Operation Warp Speed.

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On a roll, Mer­ck blazes through a new seg­ment of the bio­mark­er trail

Merck has notched an approval for using Keytruda to treat a biomarker-based subset of first-line colorectal cancer patients with unresectable or metastatic tumors, as the pharma giant continues to find new niches for its blockbuster PD-1 star.

The OK is significant in a number of ways. Not only does it build on an accelerated approval for all tumors characterized as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); it also marks the first single treatment for colorectal cancer that doesn’t contain chemotherapy.