Update on antimalaria drugs
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Thousands of Covid-19 patients world-wide are signing up for studies exploring whether antimalaria drugs fight off infections of the new coronavirus, according to a Wall Street Journal review of a clinical-trial database, and thousands more patients are taking the unproven pills as part of their treatment.
Researchers studying the drugs have drawn up plans to enroll about 200,000 people to test whether the drugs could be used to prevent infections or help the sick get over them. More than 100 studies are under way, according to the analysis, which reviewed the U.S. government’s clinicaltrials.gov registry of trials and interviewed researchers.
The global efforts are seeking a long-elusive answer regarding these drugs: Could they help fight off a virus? So far, researchers in China and France studying small numbers of patients have reported they may help patients, and U.S. doctors using the drugs tout their benefits.
Yet many infectious-disease experts say there isn’t sufficient scientific evidence to determine whether taking an antimalaria pill will truly help in a safe way, especially studies comparing how patients who took the drug fared with those who didn’t.
"’Does it offer benefit?’ is the big question we want to know the answer to,” said Roy Gulick, chief of infectious diseases at New York’s Weill Cornell Medicine and NewYork-Presbyterian. “We’re not there yet.”
The most advanced studies could have results in the coming weeks, researchers said.
Citing the lack of evidence, public-health authorities and infectious-disease experts, including Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, have cautioned against coronavirus treatment with the drugs, chloroquine and hydroxychloroquine, until there is more concrete evidence.
This week, a panel convened by the U.S. National Institutes of Health recommended against using hydroxychloroquine in combination with the antibiotic azithromycin except during clinical trials. The experts cited potential heart problems the combination could cause.
The NIH also said there wasn’t sufficient data to recommend, or recommend against, using hydroxychloroquine or chloroquine alone
Many hospitals, however, are giving the drugs to Covid-19 patients in a bid to relieve breathing difficulties, while doctors are prescribing the pills to patients with mild symptoms such as cough and fever to stop the condition from worsening.
Some doctors who have been giving the drugs to Covid-19 patients swear by their benefits, and say patients can’t wait weeks or months for rigorous studies to read out.
“I don’t need anything else to convince me,” said Joseph Brewer, an infectious-disease specialist at St. Luke’s Hospital in Kansas City, Mo., who says most of the four-dozen moderate and severe patients he treated with the drugs have improved. “I’ve seen people get better in one to two days.”
The antimalarials are among dozens of drugs developed for other uses that are now under study to see if they can help tackle the new coronavirus.
Chloroquine was approved decades ago to treat and prevent malaria by fighting the disease parasite. Hydroxychloroquine, discovered later, is considered by doctors to be less toxic. Researchers later found both could reduce inflammation. Hydroxychloroquine is now approved for autoimmune diseases like lupus and rheumatoid arthritis, and chloroquine has been used for those diseases, too.
The pills can have rare side effects, including eye and heart problems, although hydroxychloroquine less so.
Researchers have repeatedly explored whether the malaria drugs could fight off viruses, from HIV to influenza and coronaviruses, but the pills never worked in humans.
Some scientists and doctors, looking for something that could help treat coronavirus cases, were drawn to the malaria pills, theorizing their anti-inflammatory properties might help contain the hyperactive immune response seen in Covid-19 patients.
The medicines’ potential for treating Covid-19 gained traction in March as President Trump praised them on Twitter and during news conferences.
One reason for the excitement: A laboratory study in China found that chloroquine could inhibit the coronavirus from entering cells, suggesting it could stop the virus. Studies in China and France testing the pills in small groups of patients found their symptoms improved and levels of the virus in the blood dropped.
Preliminary research justifies deploying the drugs to treat mild coronavirus patients, before they require hospitalization, said Peter McCullough, a cardiologist at Baylor Scott & White Health in Dallas, which is studying hydroxychloroquine as a prophylactic in health-care workers.
Patients can’t wait, he said, the years it could take to get full results from rigorous trials. “We have to make some decisions now,” he said.
Yet many infectious-disease experts question the preliminary results. They say a widely cited French study, which tested hydroxychloroquine and azithromycin in 20 patients, was flawed, partly because several patients who fared poorly weren’t factored into conclusions.
The International Society of Antimicrobial Chemotherapy, the medical society whose journal published the research, later said it fell short of its “expected standard.”
Also, some other studies haven’t found a clear benefit. In Brazil this month, part of a trial was suspended because patients getting high doses of chloroquine developed heart problems and appeared more likely to die.
An analysis of 368 patients in U.S. Department of Veterans Affairs hospitals, released this week, found that more died if given hydroxychloroquine versus standard care. The results weren’t peer-reviewed and the authors noted they only included men with a median age older than 65 years.
The Infectious Diseases Society of America and the American Thoracic Society this month advised the therapy be limited to hospitalized patients in clinical trials, citing limited research.
Unlike some of the first trials to produce results, many trials now under way compare patients getting the drug with a control group of patients who aren’t, which researchers consider the best way of evaluating whether an experimental medicine works.
Some of the trials combine the malaria pills with other drugs, while other studies are exploring different doses and frequency. Many trials are testing how they fare in nurses, doctors and other health-care workers who regularly face exposure to the deadly respiratory disease.
At the University of Pennsylvania, researchers are testing hydroxychloroquine in 400 people to see if it could work in three different scenarios: to treat cases quarantined at home, to aid hospitalized patients at either high or low doses, and to prevent infections in health-care workers.
“Health-care workers are under a lot of stress throughout this whole pandemic, and anything we can do to help lower their risk, because their exposure is pretty much continuous, they’re greatly interested in,” said Benjamin Abella, an emergency room physician at Penn helping lead the study. It may have some results by this summer.
Despite uncertainties about the benefits, some physicians say hydroxychloroquine is an appropriate medication in the absence of proven alternatives.
Vladimir Zelenko, a doctor in Monroe, N.Y., said he has treated about 400 Covid-19 patients with a regimen of hydroxychloroquine, azithromycin and zinc sulfate. Nearly all the patients avoided being hospitalized, and just two patients died, he said.
Sandoz, the generic-drug arm of Swiss company Novartis AG , plans to pump out 130 million doses of hydroxychloroquine—two years’ worth—by the end of May for government donations. To do so, it will tear through its entire supply of raw material.
“We committed everything we could make,” Sandoz Chief Executive Richard Saynor said.
