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Wednesday, December 2, 2020

Slaoui: U.S. should be able to immunize nearly 1/3 of population by end of Feb.

 The U.S. should be able to distribute enough coronavirus vaccine doses to immunize 100 million people by the end of February, President Donald Trump’s Covid-19 vaccine czar said Wednesday.

That will be enough doses to protect a “significant portion” of the most at-risk Americans, which are the elderly, health-care workers and people with preexisting conditions, Dr. Moncef Slaoui, who is leading the Trump administration’s vaccine program Operation Warp Speed, told reporters during a news briefing.

There is a chance the U.S. could have more doses than expected that month if Johnson & Johnson’s potential vaccine is authorized by then, Slaoui said, adding he expects the company to release key late-stage trial data in January.

The federal government is expected to ship 6.4 million doses of Pfizer’s vaccine to jurisdictions across the nation within 24 hours after an emergency use authorization from the Food and Drug Administration, Army Gen. Gustave Perna, chief operations officer for Operation Warp Speed, said at the same briefing. Officials plan to ship 12.5 million doses of Moderna’s vaccine following an emergency authorization, he added.

The planning “is not about getting in front of the EUA,” Perna told reporters. “It is making sure we have everything locked so when EUA decisions come, distribution to the American people becomes immediate.”

The briefing Wednesday came as states prepare to distribute a Covid-19 vaccine in as little as two weeks. Moderna and Pfizer late last month requested emergency clearances from the FDA for their Covid-19 vaccines. The reviews by the FDA are expected to take a few weeks, and the agency has scheduled a meeting for Dec. 10 to discuss Pfizer’s request for authorization.

Earlier Wednesday, the U.K. became the first country to authorize the Pfizer vaccine for emergency use, marking another step in the global battle against the pandemic.

Initial doses will be limited as manufacturing ramps up, with top U.S. health officials predicting it will take months to immunize everyone who wants to be vaccinated against Covid-19 in the United States. The federal government has deals lined up with several drugmakers to buy some of their first doses.

A Centers for Disease Control and Prevention panel on Tuesday voted 13-1 to give health-care workers and long-term care facility residents in the U.S. the first coronavirus vaccine doses once it’s cleared for public use. There are roughly 21 million health-care workers and 3 million long-term care facility residents in the United States, according to the CDC.

Medical experts have previously advocated for health-care workers to get the vaccine first, followed by vulnerable Americans -- the elderly, people with preexisting conditions and essential workers. Children and young adults are expected to get the vaccine last.

Before the vote, Dr. Nancy Messonnier, director of the CDC’s National Center for Immunization and Respiratory Diseases, said most states and local jurisdictions expect it to take three weeks to vaccinate all of their health-care workers. Pfizer’s and Moderna’s vaccines require two doses about a month apart. Both vaccines are using messenger RNA, or mRNA, technology. It’s a new approach to vaccines that uses genetic material to provoke an immune response.

Perna said Wednesday that the federal government has asked states to finalize plans for distribution by the end of this week.

States have already submitted early plans to the CDC on how they intend to inoculate some 331 million Americans against Covid-19 once a vaccine is approved. The CDC has allocated $200 million to jurisdictions for vaccine preparedness, though much of that funding hasn’t trickled down to the local level.

https://www.cnbc.com/2020/12/02/trump-covid-vaccine-czar-says-us-should-be-able-to-immunize-nearly-third-of-population-by-end-of-february.html

Colorado issuing $375 stimulus payments to residents hardest-hit by Covid

 Eligible Coloradans will soon have a little extra cash thanks to the state government.

The state has begun issuing one-time $375 stimulus payments to residents needing the most financial help, the governor’s office announced Wednesday morning.

“Whether you’ve suffered from the virus itself, faced economic struggles, or felt the mental toll -- no one is left unscathed by this pandemic. This direct cash payment will help cover rent or put food on the table for over 400,000 Coloradans who have struggled, but we know that Colorado or any state can only do so much, and national help is urgently needed,” said Gov. Jared Polis. “I’m thankful for the partnership of legislative leadership and the legislature’s efforts this week to provide real relief to Coloradans and our small businesses. We see light at the end of the tunnel with news of a vaccine, but the consequences of this pandemic will be far lingering if Washington fails to act.”

As outlined by Polis when he first announced the plan in October, any Coloradan who was eligible to receive between $25 and $500 in weekly unemployment insurance benefits between March 15 and Oct. 24 qualifies for this stimulus payment. That includes residents who received payments from the Pandemic Unemployment Assistance (PUA), Pandemic Emergency Unemployment Compensation (PEUC), or other similar programs. The state says all eligible claimants will receive an email or call from the Colorado Labor Department.

The only action claimants need to take is logging into their benefits account to make sure their selected payment method and address are up to date.

https://www.kktv.com/2020/12/02/colorado-begins-issuing-375-stimulus-payments-to-residents-hardest-hit-by-pandemic/

Considerations for Authorization of Pfizer's COVID Vax

 A rainbow is on the horizon, as we anticipate that the FDA will issue an emergency use authorization (EUA) for the Pfizer-BioNTech candidate COVID-19 vaccine, following an advisory committee meeting scheduled for Dec. 10. Based on data from the phase III placebo-controlled trial, the Pfizer-BioNTech vaccine is reported to have an overall efficacy rate of 95%, consistent across age, gender, race, and ethnicity demographics; and the observed efficacy in adults over 65 years of age was over 94%. The trial involved more than 43,000 participants (with a 1:1 randomization to vaccine or placebo) and a total of 170 confirmed cases of COVID-19 were evaluated, with 162 observed in the placebo group versus eight in the vaccine group.

Vaccine efficacy is a measure of the performance of the vaccine under "ideal and controlled circumstances" as in a research study -- a randomized controlled trial, whereas effectiveness refers to its performance under "real-world" conditions, where other variables come to bear, allowing for a pragmatic evaluation. A critical consideration is that the primary efficacy endpoint of this phase III trial was the development of symptomatic COVID-19 infection; therefore, participants who may have developed asymptomatic coronavirus infection (after receiving the vaccine or placebo) were not identified or accounted for in this study. Consequently, if an EUA is issued, the FDA will have to be clear about the spectrum of COVID-19 infection that this vaccine is efficacious against, noting that asymptomatic transmission is a key driver of the spread of COVID-19.

In deciding whether to recommend authorization, advisory group members will address the following overarching questions:

1. Based on the totality of scientific evidence available, including data from adequate and well-controlled trials, is it reasonable to believe that the candidate vaccine may be effective to prevent SARS-CoV-2 infection?

2. Do the known and potential benefits of the candidate vaccine outweigh the known and potential risks of the candidate vaccine?

The adequacy and overall quality of the evidence will come under scrutiny from multiple angles, including attention to statistical power, which refers to the probability that the trial will detect a particular effect, if it truly exists. Power is a function of multiple factors but strongly linked to sample size, and adequate power is necessary in order to differentiate between an actual vaccine effect and a difference occurring by chance.

According to the Pfizer-BioNTech study protocol, the sample size is sufficient to provide 90% power to conclude that the true vaccine efficacy is greater than 30%, which is the lower bound required by the FDA for estimating vaccine efficacy using appropriate confidence intervals. Of note, however, is that the power of this phase III trial was calculated to detect an overall effect for vaccine efficacy, and does not specifically account for subgroup differences by age, gender, race, and ethnicity. Such subgroup analyses will require multiple comparisons, and if this component of the study is underpowered, that could increase the probability of obtaining biased and spurious subgroup differences in vaccine efficacy, even with multiplicity adjustment.

Regarding vaccine reactogenicity, the companies' topline announcement said the vaccine was well tolerated across all populations with no serious safety concerns. The only grade 3 (severe) adverse events or side effects were fatigue at 3.8% and headache at 2.0%. No statistical data were reported for the frequency of mild (grade 1) and moderate (grade 2) adverse events. A previous, smaller study of this vaccine noted frequent occurrences of adverse effects encompassing injection site pain, fever, chills, headaches, and fatigue, which were primarily mild or moderate, and these are recognized as common side effects of vaccines.

This phase III trial sought to blind participants to whether they received the vaccine or placebo. However, it is reasonable to assume that given the widespread awareness of common vaccine side effects, those who had that experience may have associated it with receiving the vaccine and hence become unblinded, and this could potentially confound the study outcome, resulting in biased estimates of vaccine efficacy. Those in the placebo group could have been similarly affected by associating the absence of vaccine side effects with receiving the placebo. Experimental studies without adequate and appropriate blinding tend to show larger treatment effects than studies with proper blinding. Therefore, performance and observer bias cannot be ruled out.

Based on the evidence available in the public domain, at this time, the general expectation is that the FDA will issue an EUA for this candidate COVID-19 vaccine, with the caveat that the evidence supports that the vaccine can protect against symptomatic disease, but it is not known if it prevents infection and transmission. The FDA may be less inclined to make any recommendation or determination regarding vaccine efficacy for specific subgroups. Additional prospective data are required to determine the level of effectiveness of this vaccine including subgroup differences, the durability of its protection, as well as to monitor safety and tolerability.

Rossi A. Hassad, PhD, MPH, is an epidemiologist and professor at Mercy College, in Dobbs Ferry, New York. He is a member of the American College of Epidemiology and a fellow and chartered statistician of Britain's Royal Statistical Society.

https://www.medpagetoday.com/infectiousdisease/covid19/89964

FDA approval tracker: November

 Last month was big on FDA knockbacks, with the coronavirus pandemic playing a major part. Five complete response letters were disclosed due to chemistry, manufacturing and control issues, and there were two Pdufa delays as travel restrictions hampered manufacturing inspections. The new Pdufa date for one of the delayed projects, Bristol’s lisocabtagene maraleucel, has not yet been announced and the company is edging ever closer to the CVR deadline of December 31. On the approval side, Alnylam’s Oxlumo was given the green light a week early; it is used to treat primary hyperoxaluria type 1, a rare genetic disease. Another rare disease player, Rhythm, received its first ever approval: Imcivree gained the thumbs up in pro-opiomelanocortin deficiency obesity and leptin receptor deficiency obesity. However, only around 30 patients have been identified and Rhythm does not plan to deploy a salesforce yet. Phase III data are due soon in the bigger indication of Bardet-Biedl syndrome and there are plans for a basket trial to expand into additional genetically defined obesities. Three emergency use authorisations were granted for Covid-19 treatments last month, but all eyes are on December when two vaccines could get FDA backing.

Notable first-time US approval decisions in November
ProjectCompany2026e sales by indication ($m)OutcomeReason for CRL/delay?
Liso-cel/JCAR017/Breyanzi Bristol Myers Squibb1,155Delayed (no new date disclosed)Manufacturing inspection delay
Imcivree (setmelanotide)Rhythm955Approved-
DostarlimabGlaxosmithkline571No decision yet (Q4 date)-
SutimlimabSanofi553CRLCMC
LIQ861Liquidia Technologies476CRLCMC
ALKS 3831 Alkermes362CRLCMC
RT002/
DaxibotulinumtoxinA/
DAXI 
Revance350Delayed (no new date disclosed)Manufacturing inspection delay
SPN-812Supernus279CRLCMC
Oxlumo (lumasiran)Alnylam253Approved ~1 week early-
Danyelza (naxitamab)Y-mabs247Approved-
ZimhiAdamis174CRLCMC
Zokinvy (Ionafarnib)Eiger99Approved-
AR19Arbor-Not disclosed (private company)-
Sources: EvaluatePharma & company releases.

 

Advisory committee meetings in November
ProjectCompany2026e sales by indication ($m)OutcomeNote
AducanumabBiogen/Eisai4,757NegativePositive briefing docs but negative panel meeting, Pdufa set for March 5 2021 (Aducanumab: this time it’s personal)
Hydexor
(CL-108)
Charleston Laboratoris/
Olas Pharma
-NegativeReceived first CRL in 2017 and negative adcom in 2018, second CRL afterwards
Sources: FDA ad com calendar, EvaluatePharma.

 

FDA issued EUAs to treat Covid-19
ProjectCompany2026e sales by indication ($m)Setting
Olumiant plus VekluryEli Lilly1,729*Confirmed Covid-19 in hospitalised patients
Bamlanivimab
(LY-CoV555) 
Eli Lilly-Mild-to-moderate Covid-19
Casirivimab plus imdevimab
(REGN-COV2)
Regeneron31Mild-to-moderate Covid-19 (The pandemic response roars on)
*Veklury received full FDA approval as a single agent in October. Sources: FDA.gov, EvaluatePharma.

 

Supplementary and other notable approval decisions in November
ProductCompanyIndication (clinical trial)Outcome
XofluzaRocheThree decisions:
1) new formulation as one-dose granules for oral suspension, 
2) for the treatment of acute uncomplicated influenza in children aged 1-12, 
3) post-exposure prophylaxis of influenza in people aged 12 and over (miniStone-2 and Blockstone)
Approved for 1) and 3), not yet approved in paediatric setting
Keytruda + chemoMerck & CoTriple-negative breast cancer (≥10% PD-L1 expressers) (Keynote-355Approved
BrilintaAstrazeneca/ Merck & CoAcute ischaemic stroke or transient ischaemic attack (Thales)Approved
ImfinziAstrazenecaFour-week fixed-dose regimen for NSCLC and bladder cancer (several trials, incl Caspian)Approved
Sources: EvaluatePharma & company releases.

https://www.evaluate.com/vantage/articles/news/snippets/us-fda-approval-tracker-november-0

How the U.K. Beat the U.S. and Europe to a Covid-19 Vaccine

Britain's first-in-the-West authorization of a Covid-19 vaccine thrusts its little-known medicines watchdog into the global spotlight -- weeks before the U.K.'s split from the European Union adds to the regulator's responsibilities.

The Medicines and Healthcare Products Regulatory Agency signed off Wednesday on a vaccine developed by Pfizer Inc. and Germany's BioNTech SE, setting in motion its rollout in the U.K. It reached a decision ahead of higher-profile watchdogs, such as the U.S. Food and Drug Administration and the European Medicines Agency.

It is the British agency's highest-profile move ahead of the Dec. 31 end to the U.K.'s transition out of the EU. After that date, the MHRA will be the regulator with the primary responsibility for drugs authorized for use in the U.K., stepping out of the shadow of the EMA, which had that role for the last 16 years.

"The MHRA has enormous incentive to appear very smooth to ensure that starting in 2021, companies will come to them with new drugs, new vaccines," said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. It is a dress rehearsal with the whole world watching, he said, and the message is: "We'll do it quickly."

June Raine, head of the MHRA, said in a televised briefing on Wednesday that the agency followed international vaccine-review standards, from deciding hurdles for safety and effectiveness in the summer to monitoring the quality of Pfizer-BioNTech doses coming out of factories in recent days. Asked about any concerns that the regulator had rushed the process, Dr. Raine said, "Everyone can be absolutely confident that no corners whatsoever have been cut."

The FDA and the EMA have defended their slower approach. Both agencies have rapidly compressed their own typical vaccine-approval timelines, and both are expected to make a decision on the Pfizer vaccine this month.

The FDA on Dec. 10 will hold an online public meeting, with expert advisers, to discuss emergency-use authorization of the vaccine. Scientists and other members of the public can submit comments beforehand. The next day, the EMA will host a virtual public meeting to talk about vaccine development and regulatory reviews.

Such meetings -- designed to bolster confidence in the regulatory process -- require extensive time and planning. Researchers say they might help address people's hesitancy to take vaccines. The FDA is expected to make a decision on the Pfizer shot a few days after the Dec. 10 meeting. FDA Commissioner Stephen Hahn told ABC News on Tuesday that the agency would take the time necessary to perform its own analysis.

The FDA scheduled the public meeting on Nov. 20, in part to assure the public it wasn't being rushed by political considerations. It is expected to rule on a vaccine from Moderna Inc. a short time after it makes a call on the Pfizer shot.

The EMA said Wednesday that it was pursuing a broader category of authorization, which would be more sweeping and permanent than the British decision. EU law doesn't allow the EMA to reach the kind of temporary, emergency-use authorization that the U.K. pursued, agency officials said. As such they needed more evidence and assurances that manufacturing controls will remain in place after authorization, they said.

"These are essential elements to ensure a high level of protection to citizens during the course of a mass vaccination campaign," an EMA spokeswoman said.

The EMA is set to announce a decision about Pfizer's vaccine by Dec. 29 and Moderna's vaccine by Jan. 12. In each case, the agency will have to convene its high-level scientific committee for human medicines before reaching a judgment. Communication between drugmakers and the EMA has been slowed by data-formatting issues and software compatibility, according to people familiar with the matter. Last week, the agency said it was willing to consider ways to speed up its system, and asked pharmaceutical companies to make suggestions.

The U.K. agency has the advantage of having been a workhorse of the EMA during the country's time in the EU, handling evaluations for a large chunk of the overall bloc's new medicines. Individual EU countries oversee clinical trials; the EMA enforces guidelines for safety, effectiveness and quality, and coordinates bloc-wide decisions, via committee, on authorized use.

The U.K.'s decision to leave the EU pushed the EMA last year to move out of its London headquarters and set up shop in Amsterdam.

The EMA by then had already been doling out the U.K. regulator's massive portfolio of Europe-wide medicine evaluations to other EU countries. The 370 medicines at the time that were part of the U.K.'s responsibility were redistributed among 27 EU nations plus Iceland and Norway, the EMA has said.

With its workload lessened, the MHRA "has been relatively underworked," said Prof. Evans. That has given it additional bandwidth to act quickly, researchers said. The London-based MHRA also gained experienced staff who left the EMA and stayed behind in the city.

British regulators and ministers also no longer need to go through the EU committee system. "There is an advantage in being small," said George Freeman, a former U.K. life-sciences minister who oversaw MHRA changes to speed up drug reviews.

The agency -- not a household name even in its home country -- was founded in 2003 with the merger of separate U.K. regulators for medicines and medical devices, and has a staff of 1,320. The EMA has about 900 employees, though it doesn't evaluate medical devices or oversee clinical trials. The FDA has a staff of around 17,000.

For the vaccine green light, the U.K. government used a long-held power to authorize drugs on its own in an emergency, allowing the MHRA to review the drug outside the EMA framework even before the end of the Brexit transition period. All other EU members have the same power, but none have publicly declared plans to exercise it.

Pfizer executive Ralf Rene Reinert said during a media briefing on Wednesday he was receiving emails about other countries considering pursuing more-rapid authorization, following the U.K.'s lead. "The world is at the moment looking at the U.K.," he said. He didn't name the countries.

Like the FDA and the EMA, the British agency used data from large-scale human trials handed over in rolling batches as the trials progressed. People who have been working with the MHRA in recent months say it has been more proactive in working with drug companies as they provide data, asking additional questions and requesting more information that could speed a review.

Recently, the MHRA's "rolling review is a much more interactive experience," said Sarah Blagden, associate professor of experimental cancer therapeutics at the University of Oxford, who oversees cancer trials. "The regulators become part of the discussion very, very early on."

In the run-up to the Pfizer vaccine authorization in the U.K., teams from the company and its partner BioNTech worked around the clock with counterparts at the MHRA, answering individual queries and providing extra, bespoke data when necessary, according to people familiar with the process. They said the MHRA was sending questions to the companies through last weekend.

Prof. Reinert, the Pfizer executive, said the MHRA would respond quickly, sometimes after just 10 minutes, to data it sent in.

BioNTech praised the U.K. regulator. "The MHRA has asked the same level of detail of questions as any agency," said Sean Marett, BioNTech's chief business and commercial officer.

The U.K. government has also asked the agency to review a vaccine being co-developed by AstraZeneca PLC and the University of Oxford ahead of a possible emergency-use authorization. The U.K. has said it is doing rolling reviews of trial data from the shot by Moderna, too, and that the vaccine, if authorized, could be available in the U.K. as early as the spring, similar to the rest of Europe.

https://www.marketscreener.com/quote/stock/PFIZER-INC-23365019/news/How-the-U-K-Beat-the-U-S-and-Europe-to-a-Covid-19-Vaccine-31921580/

NY to Get Enough Doses of Covid-19 Vaccine for 170,000

 New York expects to receive enough doses of a Covid-19 vaccine on Dec. 15 to begin immunizing 170,000 people, Gov. Andrew Cuomo said Wednesday.

Mr. Cuomo said at a news conference that the initial batch of vaccines -- manufactured by Pfizer Inc. in partnership with BioNTech SE -- will be distributed to residents of nursing homes and staff in those facilities. The companies will send the necessary second doses of the medicine roughly three weeks later to fully inoculate those recipients.

A second tranche of vaccines developed by Moderna Inc. is expected later in December, state officials said. Both Pfizer and Moderna have asked the Food and Drug Administration to authorize use of their vaccines, and the distribution is contingent upon that approval.

The initial number of doses won't be sufficient to fully inoculate the 85,000 nursing-home residents and 130,000 facility staff in the state, officials said. However, the governor said he expects some individuals will decline to take the vaccine.

Mr. Cuomo, a Democrat, said he was following the advice of a federal advisory panel that on Tuesday recommended that health-care workers and residents of long-term care facilities be the first to receive vaccine doses. The governor said hospital-based health-care workers in the state would be vaccinated after people who live and work in nursing homes.

Under the plan Mr. Cuomo outlined, the majority of the state's more than 19 million residents won't receive a vaccine for months. Between 75% and 85% of residents must be vaccinated for normal economic activity to resume in the state, Mr. Cuomo said.

The state faces serious challenges in distributing vaccines and building public buy-in for vaccination programs, the governor said. Given those challenges, and the limited supply of vaccines, he said he expects a critical mass of New Yorkers to be inoculated by as early as June or as late as September.

The governor said the arrival of vaccines in New York offers both hope and challenges as the state has seen a sharp rise in the number of Covid-19 cases and hospitalizations in recent weeks.

"That's the bad news; we have another mountain to climb," Mr. Cuomo said. "The good news is, the goal line is in sight and the goal line is a vaccine."

The recent surge in cases is being fueled by residential gatherings -- many related to the holiday season -- and may begin to slow and reverse by mid-January, Mr. Cuomo said.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/New-York-Will-Get-Enough-Doses-of-Covid-19-Vaccine-for-170-000-People-Update-31922880/

Medical journal editorial refutes WHO finding on Gilead's remdesivir for COVID-19

 An editorial in the influential New England Journal of Medicine cites problems with a World Health Organization (WHO) study that found Gilead Sciences Inc's antiviral remdesivir failed to improve COVID-19 survival, and said it does not refute trials that demonstrated benefits of the drug in treating the illness.

The editorial, by David Harrington at the Harvard T.H. Chan School of Public Health, infectious disease specialist Dr. Lindsey Baden and Brown University biostatistician Joseph Hogan, was published on Wednesday along with the WHO study.

They noted that the trial called Solidarity, which looked at four drugs, was conducted in 30 countries ranging from Switzerland and Germany to Iran and Kenya, leading to inconsistencies in the data collected.

The findings are complicated by the fact that there is "variation within and between countries in the standard of care and in the burden of disease in patients who arrive at hospitals," they write.

Solidarity also found no COVID-19 survival benefit from treatment with the HIV drug lopinavir, the immune booster interferon or hydroxychloroquine, a malaria drug championed by U.S. President Donald Trump despite a lack of evidence of benefit in COVID-19.

The release in October of the trial's summary findings sparked a reevaluation by some of the utility of remdesivir, which was shown to shorten COVID-19 hospitals stays by five days compared with a placebo in an earlier U.S. government-run trial.

Solidarity "did not collect or report the standard of care or the healthcare system capacity in any of the 400 hospitals from 30 countries," said Dr. Andre Kalil, infectious disease specialist at the University of Nebraska Medical Center and lead investigator of the U.S. trial.

"If the basic supportive care is scarce or inadequate, no treatment drug will show much benefit even if known to be effective, because the adequate supportive care is essential for the survival of patients hospitalized with COVID-19," he said.

The WHO last month declared that remdesivir, which is given as an intravenous infusion, should not be used for patients hospitalized with COVID-19, regardless of how ill they are, since there is no evidence that it can improve survival or reduce the need for mechanical ventilation.

The U.S. Food and Drug Administration in October approved remdesivir, which is sold under the brand name Veklury, for COVID-19 patients over the age of 12 who require hospitalization. The drug is authorized or approved for use as a COVID-19 treatment in more than 50 countries.

Both the U.S. Infectious Diseases Society of America and the National Institutes of Health, which conducted the U.S. study, in recent weeks reaffirmed their guidelines for use of remdesivir following the FDA's full approval of the drug.

https://www.marketscreener.com/quote/stock/GILEAD-SCIENCES-INC-4876/news/Gilead-Sciences-Medical-journal-editorial-refutes-WHO-finding-on-Gilead-s-remdesivir-for-COVID-19-31924327/