Chloroquine, hydroxychloroquine and COVID-19

UPDATE: In June 2020, the World Health Organization (WHO) and the US National Institutes of Health (NIH) halted the hydroxychloroquine arm of the Solidarity trial and the ORCHID study, respectively, after results showed that hydroxychloroquine provided no benefit to hospitalized patients with COVID-19. Previously hydroxychloroquine trials had been temporarily halted over safety concerns following the publication of a multinational registry analysis in May 2020. However, the authors of the analysis later retracted their paper after the veracity of the data they used was questioned and an independent third-party peer review could not be conducted. Hydroxycholoquine trials resumed briefly after the analysis was retracted, but were stopped again after results indicated the drug was not effective.

March 21, 2020

• US to investigate chloroquine, an old antimalarial drug with a known safety profile

• Clinical trials of chloroquine and hydroxychloroquine, a less toxic derivative of the drug, are already underway in other countries

• Chloroquine has been shown to be highly effective at controlling the new coronavirus infection in in vitro laboratory tests

• Hydroxychloroquine is more potent than chloroquine in vitro

Chloroquine (Resochin) and hydroxychloroquine (Plaquenil) have been under investigation as potential treatments for COVID-19, the disease caused by the new coronavirus (SARS-CoV-2). However, they have attracted more attention following US President Trump’s announcement that chloroquine would be made available in the US for COVID-19. Stephen Hahn, the FDA Commissioner, clarified that the FDA would be taking a closer look at chloroquine to determine whether it would be of benefit to people with COVID-19. He confirmed they wanted to conduct a large clinical trial to investigate the drug.

What are chloroquine and hydroxychloroquine?

Chloroquine is a 4-amino-quinoline compound that is already approved as an antimalarial and amebicidal drug. Hydroxychloroquine is a hydroxylated version of chloroquine. It is a less toxic metabolite, which is primarily used to treat chronic discoid lupus erythematosus and systemic lupus erythematosus, as well as rheumatoid arthritis. It can also be used to treat and prevent malaria in some cases.

Why the interest in these drugs?

Following the SARS epidemic in 2003, researchers investigated the potential of chloroquine and discovered that it was effective at preventing the spread of that coronavirus in cell culture. Researchers have since confirmed that the drug is also highly effective at controlling infection with this new coronavirus in vitro. In addition, laboratory studies have revealed that hydroxychloroquine is even more potent than chloroquine.

Chloroquine works by blocking the coronavirus from getting into cells, but it also has immuno-modulating activity that may further improve its efficacy.

These drugs are of particular interest because they are already approved for other conditions and their safety profile is well understood. Chloroquine has been used for more than 70 years and generic versions of both drugs are available at low cost.

What investigations are underway?

In early 2020, clinical trials of chloroquine for COVID-19 began in China. Chinese researchers have reported that their initial findings show the drug is effective and it has been included in the Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition) guidelines. Belgium and South Korea are also reported to have included chloroquine in their COVID-19 treatment guidelines.

The results from China showed that patients who took the drug showed improvement across a range of indicators compared with those who do not take it. Patients who took chloroquine had their fevers subside sooner, their CT lung images showed improvement, and they were quicker to test negative for the virus. Patients taking chloroquine also appeared to recover more quickly.

On March 18, 2020, the World Health Organization (WHO) announced that it will conduct multi-arm, multi-country clinical trials for potential treatments for COVID-19. Both chloroquine and hydroxychloroquine are among the drugs which will be tested.

French researchers, who conducted a small trial in 24 patients, have also reported that hydroxychloroquine is useful for reducing viral load in patients with COVID-19. They found that a combination of hydroxychloroquine and azithromycin (Zithromax), an antibacterial medication, was particularly beneficial.

What about access to chloroquine and hydroxychloroquine?

Importantly, Bayer, which manufactures chloroquine under the brand name Resochin, has donated 3 million tablets of the drug in the US. Sanofi, which markets hydroxychloroquine as Plaquenil, and Novartis have also committed to providing millions of doses of hydroxychloroquine. Other generic manufacturers are also looking to increase supplies of the drugs.