FDA Yanks Emergency Use Authorization for Hydroxychloroquine

On Monday, the US Food and Drug Administration revoked the emergency use authorization (EUA) for chloroquine and hydroxychloroquine that had allowed for supplies of the drugs in the Strategic National Stockpile to be used to treat certain hospitalized patients with COVID-19 when they were not able to participate in a randomized trial.

The agency cited multiple factors that came out of its ongoing review, including:

• The suggested dosing regimens for the drugs are unlikely to have an antiviral effect.
• Newer studies could not replicate earlier findings of decreased viral shedding with hydroxychloroquine or chloroquine.
• Current treatment guidelines don’t recommend use of the medications in hospitalized COVID-19 patients outside of a trial setting, and the US National Institutes of Health now recommends against such use outside of a clinical trial.
• Data from the randomized RECOVERY trial show that hydroxychloroquine does not reduce 28-day mortality or have a beneficial effect on length of stay or any other outcomes in hospitalized patients.

“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency said in its announcement. “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”

Based on hints of benefit in preliminary studies, hydroxychloroquine took off as a potential treatment for COVID-19, and President Donald Trump said he was taking it as a preventive measure for a period of time. Subsequent studies have not supported that initial promise, however. In addition to its failure as a treatment for hospitalized COVID-19 patients in the RECOVERY trial, hydroxychloroquine flopped as postexposure prophylaxis in an 821-patient randomized trial. Muddying the waters, hydroxychloroquine has also been at the center of a high-profile controversy over data integrity that led to a large observational study of the agent being retracted from the Lancet by several of the study investigators.

The FDA initially granted the EUA for hydroxychloroquine and chloroquine on March 28 based on a request from the Biomedical Advanced Research and Development Authority (BARDA). The revocation also comes at the request of BARDA. 

“The totality of scientific evidence currently available indicate[s] a lack of benefit,” the FDA said.

Late Monday, the FDA also warned about a potential interaction when hydroxychloroquine or chloroquine is given with the investigational antiviral remdesivir (Gilead Sciences), saying that co-administration is not recommended because it might weaken the antiviral activity of remdesivir. “The agency is not aware of instances of this reduced activity occurring in the clinical setting but is continuing to evaluate all data related to remdesivir,” according to the announcement.