Seeking treatment

On Thursday President Donald Trump in a press conference named two anti-malarial drugs he said the government was investigating as potential treatments for COVID-19, the disease caused by the new coronavirus. Their names are chloroquine and hydroxychloroquine, and although the U.S. Food and Drug Administration has not approved the drugs specifically to treat the coronavirus, the agency has approved them to treat other ailments.

What are these drugs, and why use them on a patient with COVID-19?

Long ago—or so it seems—when we embarked on such now-rare journeys as going to a store simply to browse, my family and I loved to visit a thrift shop called Repurposed. The name described the adventures many of its items were destined for: An old picture frame might become a new home for a child’s artwork, and so on.

The shop owner’s creative mindset is analogous to what the world’s top research scientists are now doing: The drug-discovery world has essentially gone to Repurposed. It even uses the same name for its work. The Broad Institute, a collaboration between Harvard and MIT, calls one of its main projects “the Drug Repurposing Hub.” It summarizes its work thus:

The path to putting a drug on the market involves a long and exhaustive journey through basic research, discovery and optimization, preclinical development, increasingly elaborate and lengthy human clinical trials, and regulatory approval. New drugs can take more than a decade to get to market. But what if we could take thousands of drugs already approved to safely treat disease, as well as other compounds that have been studied as potential drugs, and find new uses for these old medicines?

Scientists have occasionally found those new uses by serendipity. Minoxidil, a potent treatment for high blood pressure, found new life as Rogaine after doctors noticed it often caused hair growth. That was easy to stumble upon, because high blood pressure is common in older men—who also might be bald.

Today, advanced research tools help scientists explore less obvious connections between drugs we already know about and diseases we didn’t know they could treat.

That brings us to chloroquine, a malaria treatment that readers who have visited the developing world might have already taken. It’s nothing new: Chloroquine dates to 1934, and its cousin, hydroxychloroquine, came to market in 1955. Manufacturers already produce both in massive quantities. Neither was designed to be an anti-viral treatment, but we’ve long known chloroquine has anti-viral effects. A 2003 paper published in Lancet Infectious Diseases suggested it might be effective against SARS, another coronavirus disease.

Because of that knowledge, chloroquine was a natural choice for investigators in China to try against SARS-CoV-2, the new coronavirus that causes COVID-19. Lab experiments showed effectiveness, and since chloroquine was already a well-known drug with an established safety profile, it went straight to human trials. Preliminary results from China are encouraging, and additional research in Europe is ongoing.

Why study hydroxychloroquine? As the drug’s name suggests, it’s a close relative of chloroquine. In the developed world, its advantages usually justify its higher price: It leads to fewer side effects, and it’s less toxic if overdosed. But most importantly, developed countries have a much better supply of hydroxychloroquine than of chloroquine, and they have factories that could easily produce more. Malaria is very rare in the United States and Europe, but hydroxychloroquine is a common daily treatment for rheumatoid arthritis and lupus.

A small French trial explored hydroxychloroquine—with or without an antibiotic called azithromycin—as a treatment for the novel coronavirus. The quality of the research was not ideal: It “excluded” from the analysis patients who started treatment but then went to ICU or died—a bad approach, from a research perspective. But even if we go back through the data and assume that the treatment failed in all of those “excluded” patients, the study still appears to show it was effective: Study patients were much more likely to be virus-free after six days of treatment.

(One safety note: Please don’t combine hydroxychloroquine and azithromycin at home! Together, they can easily lead to heart rhythm disturbances.)

While the science is not fully established, treatment guidelines in Korea and Italy are starting cautiously to endorse hydroxychloroquine as—essentially—“worth a try” against COVID-19 in lieu of any other proven treatment.

Bottom line: Limited evidence suggests the anti-malarial drugs chloroquine and hydroxychloroquine may help treat COVID-19. If so, it would be drug researchers’ best trip yet to Repurposed.

A shot in the dark?

Another drug President Trump named as a possible coronavirus treatment during his Thursday press conference is remdesivir, Gilead Sciences’ experimental anti-Ebola drug. A few patients received it for Ebola under “compassionate use” guidelines that allow doctors to prescribe unapproved medicines. It’s still at such an early stage of development that much of the research refers to it by its development name, GS-5734.

The first known patient to be hospitalized with COVID-19 in the United States received remdesivir after developing pneumonia, and improved shortly afterward. Did the remdesivir help cure him, or was he going to improve anyway? An ongoing clinical trial, in which COVID-19 patients in China received the drug, hopes to answer this question.