By Kristen V. Brown and Riley Griffin
A tiny trial of a malaria drug may or may not have helped several patients in France fight off their coronavirus infections. The FDA has said it needs more study. Some expert doctors are skeptical. President Donald Trump is all for it.
On Saturday, Trump again promoted the drug at a White House briefing, and retweeted a post about a small scientific study that has been making the rounds for several days. It followed Trump’s comments Friday that the drug, hydroxychloroquine, was a “game changer,” that “we’re going to be able to make that drug available almost immediately,” and noting that patients could get it from their doctor.
“This miracle cure is based on six subjects, which does not give me a great deal of confidence,” said Hank Greely, a bioethicist at Stanford University, said of hydroxychloroquine. “This study is promising, provocative and worth following-up on, but it is nothing more than that.”
Hydroxychloroquine is part of an urgent effort to find treatments for the coronavirus that in just a few months has killed more than 10,000 people around the globe, and could well prove effective. But so far, there’s little proof of that. It does have two things going for it, however: it’s already on the market, and is available as a lower-cost generic medicine.
Trump is far from the only person of influence to tout the idea that a drug for malaria may offer a treatment for a virus that has infected more than 21,000 people in the United States. The same study had already attracted attention from Elon Musk. Musk’s initial tweet on the subject was liked more than 55,000 times.
Hydroxychloroquine has, in essence, gone viral.
It’s one of a number of drugs being tested for treatment of patients with COVID-19. But since the virus is a new pathogen, there are no ready-made drugs on offer. Instead, scientists have pulled from their existing armory, throwing everything at it, and hoping something works.
“What do we have to lose?” Trump said Saturday at the White House briefing, also acknowledging that scientists in his administration have called for more study. “We’re going to find out very shortly whether or not it is going to work. I feel very confident.”
Hospitals, anticipating a surge in demand, are stockpiling the drug, and some are already treating patients with it on an off-label basis. Medical institutions are gearing up to conduct further studies. Urgent-care centers and tele-health companies have seen increasing numbers of patients requesting hydroxychloroquine as they read about it online, and patients who actually require the drugs have at times not been able to obtain them.
But as attention and demand for hydroxychloroquine mounts, there’s one thing desperately missing — solid proof it actually helps, and that it doesn’t harm patients.
“The president is talking about hope for people, and it’s not an unreasonable thing,” Fauci said at the same briefing, speaking shortly after Trump. “My job is to ultimately prove, without a doubt, that a drug is not only safe but that it actually works.”
The study tweeted out by President Trump looked at 26 patients who had been hospitalized with COVID-19 in France, and compared them to 16 patients at another facility who did not receive the treatment. Of all 26 patients that got hydroxychloroquine, six also received azithromycin, an antibiotic. The six patients who got the antibiotic appeared to clear the virus from their bodies.
“Many of the things that you hear out there are what I had called anecdotal reports,” Fauci said. “They may be true, but they’re anecdotal.”
Scientists are eager to explore any avenue that may lead to a potential treatment, and so larger studies of the drug are gearing up. Hydroxychloroquine and the more-toxic drug it is derived from, chloroquine, are also commonly used to treat rheumatoid arthritis and lupus. Neither drug has been approved by the U.S. Food and Drug Administration to treat COVID-19.
David Ho, a famed AIDS researcher based at Columbia University, said that in the study the treatment didn’t appear to actually make a difference in whether patients lived or got better. And it’s possible that the decreases in the amount of virus found were because of flaws in how samples were collected, or patients may have simply recovered on their own -- as most do.
Ho has given his laboratory over to studying COVID-19 and the virus that causes it, SARS-CoV-2.
“In a crisis like this, we need clarity,” Ho said. “Trump is doing just the opposite.”
The post retweeted by Trump on Saturday was authored by a little-known investor, entrepreneur and former biopharmaceutical analyst named Michael Coudrey, who also touted the same drug’s ability to fight HIV.
Reached on Twitter, Coudrey said he thought the study was promising but wasn’t strong enough to justify the drug’s wide use.
Fauci, asked whether the drug might be used preventatively against COVID-19, as it is with malaria, replied, “no.”
Long History
David Goldman, a pediatric infectious disease specialist at the Children’s Hospital at Montefiore, said though the French study “isn’t optimal and doesn’t constitute enough data to validate the new indication for that drug,” it still builds on years of research of hydroxychloroquine use in outbreaks of two related diseases, SARS and MERS.
For decades, researchers across the globe have investigated the effects of chloroquine on viral infections and against HIV. In the early 2000s, some found that it had the potential to inhibit the replication of the virus that causes SARS in mice, but other research subsequently cast doubt on that finding.
Goldman is currently working with stakeholders at Montefiore and the Albert Einstein College of Medicine at Yeshiva University to design a clinical trial that would evaluate hydroxychloroquine as a preventive treatment in more than 600 elderly residents living in nursing homes. He said Montefiore is already treating patients infected by the new coronavirus with hydroxychloroquine.
“Nobody really knows what will work, so let’s try everything: multiple different approaches, multiple different agents, based on the limited data that we have,” he said.
Drugmakers, too, are gearing up for the potential that the drug may work. Novartis AG, Teva Pharmaceutical Industries Ltd and Bayer AG have plans to ramp up production and donate millions of tablets for U.S. pandemic response, while Mylan NV is re-starting manufacturing.
Patient Demand
Some patients, with no treatment currently approved to treat the virus, seem less interested in waiting.
Caesar Djavaherian, co-founder and medical director of Carbon Health, a tele-health company and group of 16 clinics in the Bay Area, said that every day over the past week, patients have come in requesting to try the drug.
“The president and others that have publicized this drug have really put us in a tough spot,” he said.
Chloroquine phosphate prescriptions tripled in the U.S. between Feb. 14 and March 13, according to data compiled by Bloomberg and Symphony Health, while hydroxychloroquine sulfate prescriptions, which are issued at a much greater volume in the U.S., jumped more than 12% over the same period.
Data compiled by the drug shopping website GoodRx showed that between March 1 and March 16, there was a 57% surge in demand for hydroxychloroquine and a 90% increase in chloroquine.
Doctors, Djavaherian said, are now being pressured to prescribe a drug that also risks causing significant side effects. Those can range from dizziness to life-threatening allergic reactions and eye damage. When used in combination with azithromycin, there is also some evidence it can cause heart problems.
“If someone has significant risk factors to become very ill from the coronavirus, like they are older with multiple comorbidities, the thinking is why not prescribe it?” Djavaherian said. “The studies so far have not been sufficient, but if someone were to have a bad outcome, now the question would be, ‘Why didn’t you treat them with this?’”
At this point, the drug should only be regarded as a last resort, Djavaherian said.
Dave Burke, owner of Dave’s Pharmacy in Marysville, Ohio and a state senator, estimated four doctors have tried filling hydroxychloroquine prescriptions for themselves or their family members within the past week at his pharmacy.
Burke was surprised by the first prescription he saw. When he received the second, he realized it was a trend. Then he read about Trump touting hydroxychloroquine. He has since stopped filling prescriptions for people he does not know to be taking the drug for conditions like lupus or rheumatoid arthritis.
“This is like the captain of the ship taking the only lifeboat where passengers are forced to drown,” Burke said.
