The U.S. Food and Drug Administration (FDA) has approved the use of two anti-malaria drugs (Hydroxychloroquine And Chloroquine) to treat patients infected by the new coronavirus.
On Sunday, the U.S. Department of Health and Human Services (HHS) said in a statement that chloroquine and hydroxychloroquine could be prescribed to teens and adults with COVID-19 “as appropriate, when a clinical trial is not available or feasible,” after the FDA issued an Emergency Use Authorization. (EUA) That marked the first EUA for a drug-related to COVID-19 in the U.S., according to the statement.
Currently, there are no specific drugs for COVID-19 which, as shown in the Statista graph below (accurate as of March 26), has sickened over half a million people. According to Johns Hopkins University, over 720,000 cases have been confirmed, more than 34,000 people have died, and over 152,000 have recovered since the pandemic started in China late last year.
Both chloroquine and hydroxychloroquine are used to treat diseases including malaria, and have “shown activity in laboratory studies against coronaviruses, including SARS-CoV-2 (the virus that causes COVID-19),” the HHS stated.
“Anecdotal reports suggest that these drugs may offer some benefit in the treatment of hospitalized COVID-19 patients. Clinical trials are needed to provide scientific evidence that these treatments are effective.”
Under the EUA, health care providers and patients must be given fact sheets outlining the known risks and drug interactions of the medications.
The HSS said it accepted 30 million doses of hydroxychloroquine sulfate from an arm of the pharmaceutical company Novartis, and one million of chloroquine phosphate from Bayer Pharmaceuticals to be used for treating hospitalized COVID-19 patients or in clinical trials.
“These and other companies may donate additional doses, and companies have ramped up production to provide additional supplies of the medication to the commercial market,” the HHS said.
“Given the importance of understanding the efficacy of these medications for the treatment and prevention of COVID-19, federal agencies, such as the National Institutes of Health and ASPR’s Biomedical Advanced Research and Development Authority (BARDA), are working together to plan clinical trials.”
The Strategic National Stockpile will ship the drugs to states, according to the statement.
The HHS said it hoped the donated drugs would “ease supply pressures” for the medications, and that it was working with manufacturers to boost production to ensure those who depend on them to treat conditions such as malaria, lupus, and rheumatoid arthritis have access.
The decision comes after FDA commissioner Stephen Hahn said that the agency would “take a closer look” at chloroquine in “a large pragmatic clinical trial—to actually gather that information and answer that question that needs to be asked and answered,” after President Donald Trump said chloroquine and hydroxychloroquine showed promise in COVID-19 patients.
Last week, the authors of a paper published in the Journal of Zhejiang University concluded that hydroxychloroquine is no better treatment for coronavirus than currently used methods.
Vineet Menachery, Assistant Professor in the Department of Microbiology & Immunology at the University of Texas Medical Branch who was not involved in the research, cautioned to Newsweek last week that the paper involved a small number of participants. And while the patients didn’t improve and it doesn’t appear to worsen COVID-19, there are concerns about its side effects.
He told Newsweek: “Like the papers to date on hydroxychloroquine and chloroquine, there isn’t much concrete data.”
As experts investigate the potential benefits of the drugs, health officials last week urged members of the public not to self-medicate, after an Arizona man who took chloroquine phosphate in the form of a fish tank cleaner died.
Ian Hall, professor of molecular medicine at the University of Nottingham told Newsweek: “I am slightly surprised by this approach, as at present we don’t know if these drugs are effective. Whilst there is some laboratory work and also anecdotal evidence in patients they may be effective, there are also preliminary trial data suggesting they may not work.
“All drugs have potential side effects, and we obviously want to avoid side effects in patients who are already ill with COVID19. Hence in my view the most important thing to do is to undertake formal clinical trials to find out if there is a role for these drugs in the management of different groups of patients with COVID-19.”
Hall said: “Ultimately we hope a vaccine will be available, and initial studies have already commenced in healthy volunteers, but it is likely to be at least six months before we may have a vaccine for wider use.”
Robin May, professor of infectious diseases and director of the Institute of Microbiology and Infection at the U.K.’s University of Birmingham, told Newsweek: “Like many things about this pandemic, the decision regarding chloroquine is a very tough one to make. Early data showed promising results with this drug, but a more recent study from China showed no evidence of efficacy. Both studies are very small, though, so the jury is still very much out.
“What is very much needed at this stage is a randomized clinical trial to establish efficacy of chloroquine—but of course, this is a challenging and long-term undertaking. In the meantime, the FDA has approved the drug for situations where alternatives are not available.”
May continued: “It is critical to emphasize, however, that chloroquine can have substantial side effects, particularly if the dosing is not correct.
“The individual risk/benefit will be something that clinicians will take into account on a patient by patient basis and consequently it is absolutely essential that patients do not self-medicate in the meantime, which can have life-threatening consequences.”
Andrew Preston, reader in microbial pathogenesis at the U.K.’s University of Bath, told Newsweek there is a sound basis for the use of the drugs, and the anti-viral effects of chloroquine have been demonstrated in a number of laboratory studies involving the close relatives of SARS-CoV-2—the SARS and MERS viruses.
“However, while providing a rationale for the FDA decision, laboratory tests on isolated cells are a long way from showing efficacy in patients,” he said.
Preston explained clinical trials “involve numbers of study participants (patients in this case) of the appropriate size to given statistically significant results.” The participants are randomly assigned the treatment or a control “in which the two groups are well matched for as many parameters as possible.” Those might include age, gender, underlying conditions, study centers like hospitals where precise care may differ, days since onset of symptoms, and medications taken.
Such steps haven’t been followed when it comes to using chloroquine or hydroxychloroquine in COVID-19 patients, he said, and therefore it has not been possible to properly determine whether either drug had an effect, or not.
“Unfortunately, proper clinical trials take time to set up and to conduct. A number are already underway, and initial results from these can be expected in the coming days and weeks,” said Preston.
Fortunately, both drugs have been used in humans, meaning doctors know they are well-tolerated, as well as the side effects and appropriate dosing levels.
“Thus, the huge concerns regarding patient safety are lifted in terms of using chloroquine and hydroxychloroquine,” he said. “In this regard, many will see it as a case of ‘can do no harm, but might do some good’ and combined with the relative cheapness of the drugs, this probably contributed to the FDA’s decision.”
Preston said: “The desperate clinical need for treatment options for COVID-19, and the pressure that authorities are under to provide answers/solutions, and to be shown to providing them, it is perhaps understandable as to why the FDA has moved to approve chloroquine and hydroxychloroquine use before the firm evidence supporting their use is available.”