The United States Food and Drug Administration decision Thursday to approve Gilead Science’s Remdesivir as a COVID-19 treatment failed to consider the results of the recent WHO “Solidarity Trial”  – which found no measurable benefits for the drug’s use – because the pharma company failed to include the study in its FDA submission for approval,  WHO’s Chief Scientist said on Friday.   

Speaking at a WHO press conference, Soumya Swaminathan also said that she hoped to see  results from “one or two” viable COVID-19 vaccine candidates emerging by the end of this year. But like other experts, she cautioned that even if all goes well, a vaccine would only likely become available in the first quarter of 2021 to the highest risk groups – like health workers. 

“Certainly in early 2021, I think we’re going to start seeing more and more results coming out.  And somewhere in the first quarter of 2021, we’re talking about the world, there may be some vaccines available for the most high-risk groups in countries around the world,” said Swaminathan, repeating a frequent WHO call that the initial, limited supplies should be fairly distributed with front-line health workers around the world getting access first.

Gilead Sciences Omitted WHO’s Evidence That Remdesivir Doesn’t Work From Its FDA Submission  

In terms of GIlead’s omission of the WHO evidence on Remdesivir, Swaminathan said that WHO provided the results of its Solidarity Trial, the largest of the drug in the world, to Gilead Pharmaceuticals on 28 September, even before they had been publicly announced on 16 October by WHO:  “but it appears that the Solidarity results were not considered, were not provided to the FDA.” 

She also said: “What we understand from the FDA decision yesterday was that it was based on data submitted to them from Gilead, which did not include the Solidarity Trial results.”  

The WHO Solidarity trial is the largest in the world to have been conducted on the experimental treatment, which was originally developed for Ebola but never approved. The WHO Solidarity Trial of the drug’s use against the SARS-CoV-2 virus that causes COVID-19 involved 5000 patients around the world, who were randomized to administration of the drug or the standard of care. 

Even though the WHO sponsored trial was not double blinded – investigators knew which patients were being administered the drug or not, it was still “very robust” Swaminathan said, “because we looked at endpoints like mortality, like death, which is not a soft endpoint. Its not something you can fudge. We looked at progression to ventilation, which is again, very objective,” she said. 

“We looked at very important endpoints, like hospital mortality. No difference. Progression to ventilation – 92% of the people who entered this trial were not on mechanical ventilation… we looked at how many of those progressed to need ventilation. There were exactly the same numbers in the Remdesivir and the control arm…. ”

The trial also looked at the proportion of patients discharged from hospital after seven days – and there again, there was “no difference in those proportions” for people receiving Remdesivir and those receiving a standard of care, she said.   

US FDA Decision Anchored in NIAID Trial

The US FDA decision Thursday, announced as the “first treatment for COVID-19” to be fully approved by the agency, appeared to be largely anchored in the results of two clinical trials sponsored by Gilead, which showed varying degrees of symptomatic improvement for people administered the drug, as well as a trial conducted by the National Institute of Allergy and Infectious Diseases (NIAID), with over 1,000 patients in spring 2020, which found slight benefits for people using the drug in terms of their “time to recovery”.  

Of the latter, the US FDA statement said the NIAID trial evaluated how long it took for subjects to recover from COVID-19 within 29 days of being treated:

“The trial looked at 1,062 hospitalized subjects with mild, moderate and severe COVID-19 who received Veklury (n=541) or placebo (n=521), plus standard of care. Recovery was defined as either being discharged from the hospital or being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care.

“The median time to recovery from COVID-19 was 10 days for the Veklury [Remdesivir] group compared to 15 days for the placebo group, a statistically significant difference. Overall, the odds of clinical improvement at Day 15 were also statistically significantly higher in the Veklury group when compared to the placebo group.

Said Swaminathan of the NIAID trial and others, “Recovery was defined in a number of ways, but it was based on how patients were feeling, whether they needed oxygen, and whether they needed hospitalization.” 

Despite Gilead Pass – WHO To Incorporate Solidarity Trial Findings in Updated Global Treatment Guidelines

Despite the fact that the Solidarity findings on Remdesivir were ignored in the US FDA approval process, WHO will be incorporating the results into an updated set of global treatment guidelines that should be issued within the next several weeks.  The Solidarity Trial also tested the efficacy of three other treatments including hydroxychloroquine, Interferon and the HIV combination drug Lopinavir-Ritonavir – all of which have fallen by the wayside as well. Conversely, WHO says, the inexpensive generic drug, dexemethasone, has been demonstrated to reduce mortality by a third among critically-ill COVID-19 patients, in a UK trial, and has been strongly recommended by WHO for use in severe and critically ill patients.   

“We believe our results are very robust, and we hope that people who are doing treatment guidelines around the world as well as regulators around the world will take note of the study results, in addition to the other evidence – because you need to look at the global evidence for a drug before you make decisions,” said Swaminathan. 

COVID-19 Infection Trends Have Countries on ‘Dangerous’ Track, Warns WHO Director General

Meanwhile, WHO Director General Dr Tedros Adhanom Ghebreyesus warned that current COVID-19 infection trends in the northern hemiphere are on a “dangerous track” -saying that countries need to choose between the “the good, the bad and the ugly” in shaping their responses.

“The next few months are going to be very tough and some countries are on a dangerous track,” Ghebreyesus warned. 

“Too many countries are seeing an exponential increase in cases and that’s now leading to hospitals and ICUs running close. or above, capacity and we’re still only in October. We urge leaders to take immediate action to prevent further unnecessary deaths, essential services from collapsing, and schools shutting again.

“As I said in February, and I am repeating it today, this is not a drill.” 

In shaping responses, countries need to “consider the good, the bad and the ugly”, he added saying that for countries that have got COVID-19 under control, “now is the time to double down”. For those countries seeing infection rates soaring out of control, he urged politicians to “make the necesssary changes and correct course; making changes when needed shows leadership and strength.”

The WHO Director General added that public support also needs to be proffered to shield households from the worst economic fallout of COVID-19: “That means if people are told to isolate or quarantine, or businesses have to close temporarily, governments need to do everything they can to assist individuals, famlies and businesses.” 

Image Credits: WHO, ChiralJon – Remdesivir 3D.