FDA Revokes Emergency Authorization for Chloroquine, Hydroxychloroquine


The anti-malaria drugs—and clinical trials assessing their benefit—have been under close scrutiny since the EUA was first granted in late March.


The US Food and Drug Administration (FDA) has revoked the Emergency Use Authorization (EUAs) for hydroxychloroquine and chloroquine in treating coronavirus 2019 (COVID-19).

The decision comes with context in a letter written by Denis M. Hinton, chief scientist of the FDA, to the Biomedical Advanced Research and Development Authority (BARDA) on Monday morning. BARDA Deputy Assistant Secretary and Director of the Medical Countermeasure Programs Gary L. Disbrow, PhD, originally wrote the FDA requesting the 2 malaria drugs be revoked of their EUAs on the basis of continuously evolving public health response information.

“We now believe that the suggested dosing regimens for [chloroquine] and [hydroxychloroquine] as detailed in the Fact Sheets are unlikely to produce an antiviral effect,” Hinton wrote. “Earlier observations of decreased viral shedding with [the treatments] have not been consistently replicated and recent data from a randomized controlled trial assessing probability of negative conversion showed no difference between [hydroxychloroquine] and standard of care alone. “

Hinton also noted that current US treatment guidelines do not recommend either drug’s use in patients hospitalized with COVID-19 outside of clinical trials. These guidelines now include those of the National Institutes of Health (NIH), she added.

“Recent data from a large randomized controlled trial showed no evidence of benefit for mortality or other outcomes such as hospital length of stay or need for mechanical ventilation of [hydroxychloroquine] treatment in hospitalized patients with COVID-19,” she wrote.

Among the trials evaluated by the FDA was a retrospective multicenter cohort of patients with laboratory-confirmed COVID-19 admitted to one of 25 participating hospitals in the New York metropolitan area.

In assessing hydroxychloroquine with or without azithromycin versus azithromycin, versus neither drug, investigators could not find significant differences in mortality when adjusting for patient demographics and illness severity.

“Compared to patients who received neither [hydroxychloroquine] nor azithromycin, risks of cardiac arrest were higher among patients receiving [hydroxychloroquine] + azithromycin, and those receiving [hydroxychloroquine] alone, although the risk estimates were not statistically significant for the monotherapy group,” Hinton wrote.

Clinical data published to both The New England Journal of Medicine and The Lancet assessing hydroxychloroquine in patients hospitalized with COVID-19 showed limited to no benefit of care, back in late May. However, both study findings would be retracted in the coming weeks due to the limitation of data made available to authors.

Nonetheless, the validity of hydroxychloroquine particularly as an option for patients hospitalized with COVID-19 has been greatly challenged in the past month. The World Health Organization (WHO) announced the suspension of the anti-malaria treatment arm in its global, real-world, ongoing Solidarity Trial to assess the effectiveness of varied COVID-19 therapies.

As the publications were subsequently withdrawn by the authors, their data was not included in the FDA memorandum.

Hinton added in her letter announcing the EUA revocation that the known safety profile of hydroxychloroquine and chloroquine has been linked to reports of serious cardiac adverse events, as well as reports of methemoglobinemia in treated patients with COVID-19. As such, it has become unreasonable to believe the known and even suggested benefits of the drugs outweigh the known and potential risks associated with its authorized use.

Any hydroxychloroquine and chloroquine distributed from the Strategic National Stockpile (SNS) under the EUA from March 28 through today remains authorized for emergency use in the treatment of any hospitalized patients who have already been administered the product during the public health emergency, as deemed necessary by an attending physician.

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