What to know about the clinical trials for remdesivir, chloroquine, and more

Scientists are scrambling to find a treatment for Covid-19. While there are no FDA-approved therapies yet, seven U.S. clinical trials listed on are currently recruiting patients infected with the novel coronavirus. Another 33 trials testing treatments for Covid-19 are ongoing, the majority of which are taking place in China. Perhaps most exciting, last week the the launch of a multi-drug clinical trial that will enroll thousands of patients from dozens of countries.

The drugs or drug combinations so far, all of which are included in the WHO trial, are the anti-malaria pills chloroquine or hydroxychloroquine, the antiviral drug remdesivir, and the HIV drugs lopinavir and ritonavir. Several of the trials also include antibiotics and immune system modifiers in combination with the antiviral drugs to try to boost the response. Here’s some information about each one.

Remdesivir

Remdesivir is a broad-spectrum antiviral drug that interferes with a virus’ ability to replicate. It was originally developed to treat Ebola but had only limited success. However, showed that remdesivir was able to successfully stop SARS and MERS — sister coronaviruses to the new strain — in both human cells and animal models. In February, Chinese scientists that remdesivir successfully blocked the novel coronavirus, SARS-CoV-2, from replicating in human cells.

Encouraged by these findings, the National Institute of Allergy and Infectious Diseases (NIAID) selected remdesivir for the in the United States, which started on February 25. The trial is being conducted at 33 hospitals across the U.S., plus four others in Japan, South Korea, and Singapore. Soon after, Gilead, the drug company that developed and manufacturers remdesivir, launched two trials — , one in — at 17 locations in the United States, Hong Kong, South Korea, Singapore, and Taiwan. Gilead is also offering on a “compassionate use basis” to people who are not able to enroll in a clinical study. Trials of remdesivir are ongoing in China, too.

Despite the early promise, the initial data on remdesivir is mixed. The first known , a man in Washington state who had recently returned home from visiting family in Wuhan, China, was treated with remdesivir on January 26 at the , not as part of a clinical trial. Within 24 hours, he started to improve.

However, a look at the first 12 U.S. patients, three of whom received remdesivir, is less encouraging. , a preprint article that has not yet been peer-reviewed, did not see a clear difference in recovery between people who had received the drug and those who hadn’t. However, in these cases the drug was not given as part of a clinical trial, and the number of people involved is very small, so it’s too soon to draw any conclusions.

Chloroquine

Chloroquine is an that also has antiviral and immune-suppressing properties. Scientists think the drug stops the novel coronavirus in two ways: raising the pH inside cells to make them less hospitable to the virus, and interfering with the receptors the virus uses to bind to the cell. The drug also alters cytokines, immune chemicals that help the body fight infection but that can wreak havoc by causing too much inflammation. Doctors believe that a hyperactive “cytokine storm” is one of the from Covid-19.

In 2005, scientists published that against the original SARS coronavirus, rescuing cells after they had been infected and protecting them from getting the virus if the cells were treated with the drug beforehand. More recently, the same study that showed remdesivir stopped the novel coronavirus in human cells also found that chloroquine suppressed the virus, too.

Excitement from these laboratory studies led researchers in China and France to give chloroquine and its sister drug, hydroxychloroquine, to people infected with the novel coronavirus. Two papers reported that the drugs helped people recover from Covid-19 more quickly. However, details in the , which gave the drug to 100 people, were scant, and there have been critiques that the was skewed because the researchers excluded people in the analysis who started on the drug but then had to be moved to the ICU, indicating they did not improve from the treatment.

The first to test hydroxychloroquine in the United States was launched March 16, using the drug as a prophylaxis to see if it can prevent people exposed to the virus from getting sick.

While scientists are cautiously optimistic about these drugs, it’s important to remember that none of them are ready for primetime.

Lopinavir and ritonavir

This antiviral drug combination was initially developed to treat HIV, but it turns out it works on other viruses as well. The drugs are given together because lopinavir breaks down very quickly on its own, and it lasts longer when paired with ritonavir.

Similar to chloroquine and remdesivir, scientists discovered in 2004 that lopinavir was at stopping the original SARS virus from replicating in human cells. When given in combination, lopinavir and ritonavir also in human patients.

In January, doctors in China began using the drug combination to treat Covid-19 through a clinical trial. Unfortunately, the study — the first major clinical trial to be published on the novel coronavirus — did not see any difference between patients who received the drug combination and those who did not. Most of the people in the trial had been sick for nearly two weeks by the time they received the drug, though, and some researchers have suggested that antiviral drugs need to be given early on during the infection to have any meaningful effect against the virus.

Other candidates

Other medications being looked at, often in combination with these antivirals, are antibiotics and drugs that regulate the immune system. The novel coronavirus is a virus, not a bacterium, but bacterial infections can flare up in the damaged lung environment — this is how people typically die from the flu — making things worse. An antibiotic can stop that from happening.

Another drug being tested is , which inhibits an immune chemical called interleukin 6 (IL-6) and is typically used to treat rheumatoid arthritis. The main cause of death from Covid-19 is an extreme inflammatory response in the lungs caused by a hyperactive immune system. The inflammatory chemicals such as IL-6 go into overdrive in an attempt to defeat the virus but end up causing more harm than good as they destroy cells in the lungs. Doctors think that dialing back the immune system at late stages of the disease could actually prevent more serious damage.


While scientists are cautiously optimistic about these drugs, it’s important to remember that none of them are ready for primetime. Data so far has been preliminary, and more testing is needed for all of them. What’s more, all of these medications can have serious side effects. One man this week in an attempt to self-medicate against the virus.

Many of these drugs are also used to treat other conditions, such as HIV and autoimmune disorders. Some people who are regularly prescribed chloroquine said they have been unable to get their medication recently because others are buying and hoarding the drug.

If you have been diagnosed with Covid-19, ask your doctor about enrolling in one of the clinical trials. Do not attempt to treat yourself.