FDA pulls emergency-use status for chloroquine, hydroxychloroquine in COVID-19

The FDA on Monday revoked the emergency-use authorisation (EUA) for malaria drugs chloroquine and hydroxychloroquine for COVID-19. According to the agency, new data, including clinical trial results, suggest the drugs "may not be effective to treat COVID-19" and their "potential benefits for such use do not outweigh…known and potential risks."

The EUA, issued in late March, permitted hydroxychloroquine and chloroquine products donated to the Strategic National Stockpile (SNS) to be used for hospitalised adults and adolescents with COVID-19, when a clinical trial was not available or feasible. The agency noted that the drugs remain authorised for emergency use "to continue to treat any hospitalised patient to whom the authorised product has already been administered during the COVID-19 public health emergency, to the extent found necessary by such patient's attending physician."

The FDA said it revoked the EUA in consultation with the US Biomedical Advanced Research and Development Authority (BARDA), which had initially requested the emergency use. BARDA's former director Rick Bright claimed in April that he was removed from his post amid "clashes with political leadership" in the Trump administration for resisting widespread use of the malaria drugs.

Insufficient antiviral effect

In coming to its decision, the FDA said agency reviewers reassessed publications that were relied upon at the time the EUA was granted, and highlighted limitations with these studies. Specifically, new analyses suggest "it is unlikely that the dosing regimens in the EUA would be able to have an antiviral effect," and that "the substantial increase in dosing that would be needed to increase the likelihood of an antiviral effect would not be acceptable due to toxicity concerns," the regulator said.

Further, it pointed to earlier reports of decreased viral shedding, but said these findings "have not been consistently replicated," while data from the largest randomised controlled trial assessing probability of negative conversion "showed no difference between hydroxychloroquine and standard of care alone." The agency also cited recent results from the RECOVERY trial being run by Oxford University indicating that hydroxychloroquine showed no benefit for mortality or other outcomes, such as hospital stay or need for mechanical ventilation, in hospitalised patients with COVID-19.

"While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the [EUA] was no longer appropriate," commented Patrizia Cavazzoni, acting director of the FDA's Center for Drug Evaluation and Research.

New NIH guidelines

The FDA decision comes shortly after a US National Institutes of Health (NIH) panel of experts revised its advice to specifically come out against the use of chloroquine or hydroxychloroquine for COVID-19, except in formal studies, with Cleveland Clinic cardiologist Steven Nissen saying "that, I'm sure, had influence on the FDA." He agreed with the decision and said he would not have granted emergency access in the first place, as "there has never been any high-quality evidence suggesting that hyrdoxychloroquine is effective" for treating or preventing SARS-CoV-2 infection, but there is evidence of potentially serious side effects.

Still, a recent study published in The Lancet reporting that hydroxychloroquine was associated with higher rates of ventricular arrhythmia and death in COVID-19 patients was retracted earlier this month after some of the authors said they could "no longer vouch for the veracity of the primary data sources" used for the paper.

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