The Food and Drug Administration announced Monday that hospitals should no longer administer hydroxychloroquine and chloroquine, the experimental COVID-19 treatments championed by President Donald Trump.
The FDA found the drugs are “unlikely to be effective” in these patients, and said it received reports of serious cardiac adverse events. “Serious” adverse events result in death, are life-threatening, or prolong hospitalization, according to FDA.
“The known and potential benefits of CQ and HCQ no longer outweigh the known and potential risks for the authorized use,” FDA Chief Scientist Denise M. Hinton wrote in a letter to Gary L. Disbrow, deputy assistant secretary at the Biomedical Advanced Research and Development Authority.
The drugs no longer meet the legal requirements of an emergency use authorization, a pathway that makes drugs available in advance of full FDA approval in emergencies, the FDA said. Health and Human Services Secretary Alex Azar must determine if the waivers of FDA regulations are warranted to “mitigate the effects of” or “reduce the severity of” a public health emergency.
“Current U.S. treatment guidelines do not recommend the use of CQ or HCQ in hospitalized patients with COVID-19 outside of a clinical trial,” Hinton’s letter reads.
The FDA also warned health care providers separately against pairing remdesivir, an experimental COVID-19 drug, with hydroxychloroquine or chloroquine, saying they could reduce remdesivir's effectiveness. Preliminary clinical trial results have indicated remdesivir can modestly speed recovery.
The Strategic National Stockpile accepted donations of chloroquine from non-FDA-approved plants to be distributed to states in March.
Under the terms of the emergency use authorization, information about outcomes experienced by patients taking the drug were required to be reported to BARDA.
Of the 1,763 patients who took the drug via the national stockpile, abnormal heartbeats were reported in six patients and other cardiac adverse events were reported in 30 patients as of May 26, according to the letter.
“We’ve made clear throughout the public health emergency that our actions will be guided by science and that our decisions may evolve as we learn more about the SARS-CoV-2 virus, review the latest data, and consider the balance of risks versus benefits of treatments for COVID-19,” FDA Deputy Commissioner for Medical and Scientific Affairs Anand Shah said in a press release.
The risks to heart health, including the risks of heart rhythm problems, have been known for weeks, and resulted in internal conflict between President Donald Trump and Azar on one side, and BARDA on the other.
The emergency use authorization was signed by former BARDA Director Rick Bright, who said he did so under pressure. He filed a whistleblower complaint in late April alleging he was forcibly reassigned in late April in part for raising safety concerns.
Part of his concerns stemmed from the Strategic National Stockpile accepting donations of chloroquine from drug plants with poor safety records, Bright said in his complaint.
Azar countered Bright’s criticism by pointing out the BARDA director had signed the document authorizing its use.
In congressional testimony in mid-May, Bright claimed he signed the EUA in order to forestall a broader “compassionate use” authorization that would have allowed patients to receive prescriptions outside of a hospital setting.
Some physicians have reported anecdotal evidence that they saw patients improve while taking hydroxychloroquine.
“I’m hearing from a lot of doctors in my state and around that country, who have experienced hydroxychloroquine and chloroquine, coupled with azithromycin or zinc, and they’re reporting significant benefit if it is used early enough in the course [of treatment],” said Rep. Michael C. Burgess, R-Texas, a physician, at the May hearing where Bright testified.
After the FDA issued a safety warning on April 24 that the drug could cause severe heart rhythm problems in COVID-19 patients, demand for the stockpile’s supply dropped. Hospitals like the Mt. Sinai Health System in hard-hit New York City reported they had stopped using hydroxychloroquine for the disease.
Demand for the drug by Texas hospitals dropped off to zero, according to data released by the state’s public health department. Some states distributed their newly acquired supplies to rheumatoid arthritis or lupus patients who used them for those FDA-approved needs and who experienced a shortage after Trump touted the drugs.
Many clinical trials are studying the effectiveness of hydroxychloroquine and chloroquine as a treatment or preventive drug for COVID-19. The FDA’s revoked authorization allowed the drug to be taken outside of these trial settings.
The World Health Organization is conducting a multi-country clinical trial studying hydroxychloroquine. The WHO temporarily stopped the trial in light of a study published in The Lancet, but the trial was resumed and the study was later retracted.
Mike Ryan, executive director of the WHO Health Emergencies Programme, said the executive group would meet this week and continue to look at the data.