By Sravya Chary
Experts are calling into question the recent decision of the U.S. Food and Drug Administration (FDA) to approve remdesivir (sold under the brand name Veklury) for the treatment of COVID-19 and casting scrutiny as to whether the decision is truly in the public’s interest.
Evaluating and approving an effective treatment for SARS-CoV-2 virus has been a top priority for regulatory authorities, especially in the absence of a viable vaccine. On October 22, 2020, the FDA approved Veklury for the treatment of COVID-19 in adult and pediatric patients requiring hospitalization.
The FDA cited three randomized, controlled clinical trials as the evidence supporting its decision to approve Veklury. The findings from the three studies were as follows: first, that the median time to recovery from COVID-19 was 5 days sooner in the Veklury group compared to the placebo group. Second, that the odds of a research subject’s COVID-19 symptoms improving were statistically significantly higher in the five-day treatment group than the standard of care group (the 10-day treatment group did not show a statistically significant difference from the standard of care group). Third, that there were no statistically significant differences in recovery or mortality rates between subjects in the five-day Veklury group versus the ten-day Veklury group.
Reasons Behind Experts’ Skepticism
Although the evidence is seemingly promising, experts have cited the following as reasons for skepticism about the FDA’s decision to approve Veklury for the treatment of COVID-19:
Some experts scrutinized the validity of the evidence used to support the FDA’s decision. Dr. Eric Topol, founder and director of the Scripps Research Translational Institute, stated that he was “[not] supportive of this decision at all” and deemed the usefulness of Veklury in the treatment of hospitalized COVID-19 patients as unresolved.
How can Remdesivir get a full @US_FDA approval when there are such mixed data? Not supportive of this decision at all.
Does it work early? Does it work late? Does it work anytime?
So much unresolved. https://t.co/o8UDj3MMS5
— Eric Topol (@EricTopol) October 22, 2020
Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering, expressed concern in his reply tweet stating “[of] the three included studies, one lacked control, two lacked blinding, all three lacked inclusion of current standard of care, results mixed […]”
Agreed, astonishing. Of the three included studies, one lacked control, two lacked blinding, all three lacked inclusion of current standard of care, results mixed, and an entirely negative real world RCT was larger than these put together. 'Effective'? What? https://t.co/2OmX0eDZGw
— Peter B. Bach, MD (@peterbachmd) October 22, 2020
WHO SOLIDARITY Trial
In addition to criticizing the clinical trials cited by the FDA as evidence and justification for the approval of Veklury, many experts drew attention to a study conducted by the World Health Organization (WHO), which showed no evidence of the treatment’s usefulness.
Just a week before the FDA announced the approval of Veklury, WHO announced preliminary results for its study, the Solidarity Trial, which recruited 11,266 adults in 405 hospitals across 30 countries, making it the largest COVID-19 treatment study in the world. The interim trial results found that Veklury, along with other regimens, “[…] appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay.”
The results of this trial put the evidence cited by the FDA into question. Further, the largest of the three trials previously mentioned only included 1,062 hospitalized patients, a strikingly low number compared to the 11,266 adults recruited for the WHO Solidarity Trial.
Quick FDA Approval
The FDA stated in a news release that it granted Veklury Fast Track and Priority Review designations. Experts including Alexander Gaffney, the head of Life Sciences Regulatory Research at POLITICO’s AgencyIQ, have commented on just how quick the review process was.
First, the FDA's review of Veklury was FAST.
Like, almost record-setting fast–just 76 days in total.
Based on AgencyIQ's data going back to 2011, there has been only one New Molecular Entity approved more quickly (Blincyto, in 75 days).
— Alexander Gaffney (@AlecGaffney) October 26, 2020
Others have commented how this quick review process seems of a piece with the FDA’s controversial COVID-19 response thus far. Consider the regulatory agency’s decision to grant an emergency use authorization (EUA) for hydroxychloroquine in March of 2020 just to revoke the EUA in June (just months later) as the drug posed the risk of heart rhythm problems while simultaneously “[showing] no benefit for decreasing the likelihood of death or speeding recovery [in hospitalized COVID-19 patients].”
Finally, the expedited review process based on mixed evidence may complicate further research. Dr. Topol expressed concern over the increase in cost and complexity of trials for new therapies as they will now have to be compared against Veklury and a placebo. Further, trial recruitment for subsequent investigational therapies will be increasingly difficult as people become reluctant to risk the chance of getting a placebo when a drug is available on the market.
The Silver Lining
Although there are many concerns regarding the efficacy of Veklury in the treatment of COVID-19, some remain hopeful. Dr. Greg Huhn, Cook County Health Infectious Disease Specialist, believes the treatment is likely to make a significant difference in the lives of COVID-19 patients and expressed excitement in moving forward with the medication. Dr. Huhn specified that to receive the drug, patients must have evidence of pneumonia, and indicated that the earlier the drug is administered to patients, the better their chance of avoiding complications down the line.
Ongoing studies are currently underway, with the eventual goal of making the drug available to individuals in an outpatient setting via a nebulizer or inhaler. In the meantime, monitoring and adverse event reporting are vital to better understanding this new COVID-19 therapy and determining whether or not the FDA’s decision is in the public’s best interest or just another snap decision-making failure.
The above opinions are wholly my own and in no way represent the opinions of my associated institutions.