- The Food and Drug Administration on Monday revoked its emergency authorization of the malaria pill hydroxychloroquine for use against COVID-19, determining the drug is "unlikely to be effective" in treating the infectious disease.
- In a statement, the FDA said the known and potential benefits to treatment with the decades-old generic drug did not outweigh its risks, which include potentially serious disruptions to heart rhythms. Once proclaimed a "game changer" by President Donald Trump, hydroxychloroquine was initially adopted widely by physicians desperate for COVID-19 treatment options, but then fell out of favor as evidence against it accumulated.
- Pressure on the FDA increased after two large, controlled studies found hydroxychloroquine no better than standard treatment for COVID-19, strongly suggesting that early findings supporting the drug were either confounded or misleading.
The FDA's decision caps a three-month span in which hydroxychloroquine was vaulted into the global spotlight as a potential therapy for coronavirus disease.
Its rise was fueled by a jumble of conflicting studies and anecdotal reports, some of which pointed to powerful antiviral effects. The drug's potential was quickly seized on by officials in the Trump Administration, who sought to make it broadly available to Americans before researchers could gather more definitive evidence supporting its use.
Career scientists, however, were concerned about potential safety risks and weren't convinced of the drug's benefit, according to a whistleblower complaint from Rick Bright, the former director of the Biomedical Advanced Research and Development Authority. The emergency authorization granted by the agency at the end of March was a compromise, Bright said, designed to "rein in" the administration's aggressive promotion of the drug.
Six weeks later, the risks feared by FDA scientists look much clearer, especially in older patients, and the potential benefits much more suspect.
In a June 15 letter, Denise Hinton, the FDA's chief scientist, cited additional research conducted by FDA staff, changing treatment guidelines and recent study results in revoking the emergency use authorization, or EUA.
A trial in the U.K., dubbed RECOVERY, factored heavily in the FDA's decision. Results, disclosed by study investigators in early June, showed treatment with hydroxychloroquine didn't help patients hospitalized with COVID-19 survive or recover faster any more than did usual care.
RECOVERY, which is also testing other potential drugs for COVID-19, compared the outcomes of some 1,500 patients given hydroxychloroquine to 3,100 on standard treatment. Unlike previous, smaller studies, the trial was randomized and controlled, offering higher statistical certainty its results aren't the product of mere chance.
Another randomized trial, conducted by the University of Minnesota, found hydroxychloroquine did not prevent people who had been exposed to the coronavirus from developing COVID-19.
Other clinical tests of hydroxychloroquine remain, but hopes that the drug will work have dimmed considerably. Additionally, work carried out by FDA scientists suggest that some of the initial research documenting strong antiviral properties to hydroxychloroquine was misleading, and that to have an effect on SARS-CoV-2 much higher doses of the drug would be needed.
Higher doses, however, make the risk of side effects more considerable. Both hydroxychloroquine, and a version of choloroquine that was authorized along with it, have been used for decades as anti-malarial treatments. Hydroxychloroquine is also approved for arthritis and lupus as well. Both versions are generally considered safe drugs but can cause heart arrhythmias, particularly when combined with other drugs that have the same effect.
Withdrawal of the emergency authorization means the medicines will no longer be distributed from the Strategic National Stockpile, which had accepted many donations from drugmakers of hydroxychloroquine or chloroquine variants.
While hydroxychloroquine can still be shipped across state lines for FDA-approved uses, the chloroquine variant included in the EUA cannot.
As of May 22, some 2.4 million seven-day treatment courses of hydroxychloroquine had been distributed to state and local health authorities in the U.S. The FDA said it did not have information on how many of those courses were actually used.
As hydroxychloroquine's potential for COVID-19 treatment has waned, attention has shifted to Gilead's remdesivir, which on May 1 became the only other drug thus far that the FDA has cleared for emergency use against the disease. A government-run study found the antiviral helped to speed recovery among hospitalized COVID-19 patients, but the benefit was modest at best.
Supplies donated by Gilead to the U.S. are running out quickly, however, potentially renewing the strain on hospitals dealing with COVID-19 cases.
On Monday, the FDA also warned against using remdesivir together with hydroxychloroquine or chloroquine, citing a newly discovered interaction between the drug's that could limit remdesivir's effectiveness.