Actemra by Roche
Roche’s arthritis drug Actemra is working with the FDA to start a randomized, double-blind, placebo-controlled phase 3 clinical trial to study Actemra in hospitalized patients with severe COVID-19 pneumonia caused by the novel coronavirus. Roche and its partner, U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority, plan to officially begin enrolling patients in early April in different parts of the world, including the U.S.
This combination drug, sold under the brand name Kaletra, was approved in the US in 2000 to treat HIV infections. Abbott Laboratories developed lopinavir specifically to inhibit the protease of HIV, an important enzyme that cleaves a long protein chain into peptides during the assembly of new viruses. Because lopinavir is quickly broken down in the human body by our own proteases, it is given with low levels of ritonavir, another protease inhibitor, that lets lopinavir persist longer.
Ritonavir/Lopinavir + Interferon Beta
World Health Organizations SOLIDARITY study will have an arm that combines two antivirals drugs Ritonavir/lopinavir with interferon-beta, a molecule involved in regulating inflammation in the body that also has shown an effect in marmosets infected with MERS. A combination of the three drugs is now being tested in MERS patients in Saudi-Arabia in the first randomized controlled trial for that disease.
Chloroquine and Hydroxychloroquine
Hydroxychloroquine has already demonstrated the ability to kill or reduce the coronavirus in laboratory petri dishes, so the next step is to perform a patient trial. Researchers in Marseilles, France are currently performing the first patient trial of Plaquenil for COVID-19. The results have not yet been published, but the initial findings are available to the public. The drugs work by decreasing the acidity in endosomes, compartments inside cells that they use to ingest outside material and that some viruses can coopt to enter a cell. But the main entryway for SARS-Cov-2 is a different one, using its so-called spike protein to attach to a receptor on the surface of human cells. Studies in cell culture have suggested chloroquines have some activity against SARS-CoV-2, but the doses needed are usually high—and could cause serious toxicities.