When the Food and Drug Administration approves a new treatment or vaccine, as doctors we are assured that rigorous studies have proven it to be safe and effective. But the F.D.A.’s haphazard issuance of emergency use authorizations for Covid-19 treatments like hydroxychloroquine and convalescent plasma, whose potential benefits have not yet been backed up by data, has undermined this trust.
Early in the pandemic, the agency awarded an emergency use authorization for the antiviral drug remdesivir, based on evidence suggesting that it may be effective. Then last month, despite conflicting evidence, the F.D.A. prematurely granted its first full approval for Covid-19 treatment to remdesivir, now marketed as Veklury.
In early October, The New England Journal of Medicine published a report on the results of a trial funded by the National Institutes of Health that found that remdesivir decreased recovery time in Covid-19 patients who were hospitalized with less severe illness, but did not curb mortality. Other studies have shown no benefit, including the World Health Organization’s Solidarity trial, released as a preprint on Oct. 15.
Based on these results, the European Society of Intensive Care Medicine is now recommending that the drug not be routinely used in hospitalized Covid-19 patients. Infectious disease experts have stated that after examining all available evidence, we can reasonably conclude only that remdesivir may work.
Some have argued that the approval of Veklury is justified even if it is only mildly effective because there are no other proven therapies for Covid-19. This fails to acknowledge, however, the proven effectiveness of drugs like dexamethasone, a cheap and widely used steroid.
It also ignores years of assault on F.D.A. evidentiary standards, accelerated by the passage in 2016 of the 21st-Century Cures Act. This legislation, which sped up the F.D.A.’s approval process, was based on unfounded claims that the agency was too slow and hindered patients’ access to lifesaving drugs.
The F.D.A. is now increasingly approving new drugs based on weaker evidence, relying on “surrogate measures” like changes in tumor size in lieu of more meaningful clinical outcomes such as reduced mortality or hospitalizations. Recent cancer drugs, for example, have been approved without evidence of improving overall survival. Weaker standards are a boon to pharmaceutical companies, but they can also depress the development of truly innovative and effective treatments.
The F.D.A. has tried to offset its accelerated approval of Veklury by asking its maker, Gilead, to complete 29 post-market studies to further examine the drug’s effectiveness and safety. This is more than three to four times the number typically requested. It’s unclear, however, if these studies will ever be done. One report found that, five to six years following approval, only half of post-market studies had been completed and one-fifth hadn’t even been started.
Veklury’s approval could also have a chilling effect on the F.D.A.’s ability to issue emergency use authorizations for other potentially effective Covid-19 treatments, as the agency’s guidance requires there be “no adequate, approved and available alternative” for the disease. Just last week, the F.D.A. granted an authorization to an antibody treatment called bamlanivimab, for use in non-hospitalized patients with Covid-19 who are at the highest risk of developing severe disease. This may have been possible only because Veklury was approved specifically for hospitalized patients.
Veklury’s questionable effectiveness is even more problematic given the drug’s price. A course costs $3,120 — a huge price tag, and one that ignores the substantial public investment in the drug’s development.
Remdesivir predates this pandemic. It was first considered as a potential treatment for Ebola, and was developed through a longstanding partnership between the U.S. Army and the Centers for Disease Control and Prevention. It was repurposed for Covid-19 after multimillion-dollar trials sponsored by the N.I.H. suggested it could work against coronaviruses.
Despite Veklury’s questionable effectiveness, the F.D.A. has also awarded Gilead a “priority review voucher” worth $75 to $100 million. This voucher can be used by Gilead or sold to a different manufacturer to hasten review of another drug application. This would perpetuate the entry of other treatments that are hurriedly reviewed and, like remdesivir, may be of uncertain benefit.
The dangers posed by the F.D.A.’s rush in approving Veklury are compounded by the chaos of presumed political interference by the Trump administration. But the weakening of F.D.A. standards will most likely continue under the Biden administration. When he was vice president, Joe Biden strongly endorsed the 21st-Century Cures Act, and some in Congress are already pushing for its next iteration, Cures 2.0.
If passed, it would further erode the F.D.A.’s evidentiary standards. Among Cures 2.0 proposals is moving the basis for approval away from randomized, controlled trials, long considered the gold standard of evidence, and instead relying more on observational evidence and surrogate measures.
It is hard to ask people to wait for the evidence when there’s a treatment that could hold some promise, especially during a devastating pandemic. But the hasty approval of expensive new treatments like remdesivir isn’t the solution. Doctors like us must feel confident that the drugs approved by the F.D.A. are worth prescribing to our patients.
Ravi Gupta (@rgupta729) is an internal medicine physician and a fellow at the National Clinician Scholars Program at the University of Pennsylvania. Reshma Ramachandran (@reshmagar) is a family medicine physician and a fellow at the National Clinician Scholars Program at Yale University. They are both members of the Doctors for America Drug Affordability Action Team.
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