Seeking New COVID-19 Therapeutics, WHO Expands its Solidarity Study to Include Three Licensed Drugs

Expanding its existing Solidarity trial, the World Health Organization (WHO) will test three additional anti-inflammatory drugs as potential treatments for COVID-19.

Solidarity PLUS will determine whether artesunate, imatinib and infliximab — all of which are already approved for other indications — might reduce the risk of death or hospitalization in patients with the disease, WHO reported. An independent expert panel selected the candidate medications, which will be donated by the manufacturers.

Ipca’s Larinate (artesunate) is derived from artemisinin, an antimalarial extracted from the herb Artemisia annua. Artemisia is the source of several antimalarial and antiparasitic drugs with a 30-year history; all are considered very safe. Artesunate exhibits immunomodulatory, anticarcinogenic and antiviral as well as antimalarial activity.

Novartis’ Gleevac (imatinib), a tyrosine kinase inhibitor, is a first-line therapy for chronic myeloid leukemia and also used for gastrointestinal stromal tumors. In June, Dutch researchers published a randomized study using imatinib in hospitalized COVID-19 patients. Although it didn’t meet its primary endpoints of need for and duration of ventilation, the study did suggest that imatinib might reduce mortality, potentially by upregulating antiviral response genes and reducing pro-inflammatory cytokines, chemokines and vascular adhesion molecules.

Johnson and Johnson’s Remicade (infliximab) is an inhibitor of tumor necrosis factor alpha (TNF alpha). It’s FDA-approved for the treatment of autoimmune disorders, including Crohn’s disease, psoriasis and rheumatoid arthritis. A 2020 German study found that COVID-19 patients taking infliximab for autoimmune disorders were less likely to mount the potentially deadly cytokine storm.

Solidarity PLUS will be conducted in 52 countries and will enroll as many patients as possible. Patients must be at least 18 years old and hospitalized with lab-confirmed COVID-19. They will be randomized to one of the three study drugs along with standard care. Although considered an open-label study, neither physicians nor patients will know to which drug they are assigned.

The primary outcome is in-hospital, all-cause mortality. Secondary outcomes are the need for ventilation and duration of hospital stay in the overall population, as well as in the low- and high-risk patient groups.

The WHO made it clear that blockbuster findings aren’t anticipated. “It is not expected that any of the treatments currently being tested will have a large effect on the risk of death, but if any had just a moderate effect and was widely practicable then this could avoid large numbers of deaths,” the agency said. “Conversely, demonstration that certain agents have no material effect on major outcomes would be of  value.”

The study’s initial incarnation, Solidarity, found no evidence that remdesivir, hydroxychloroquine, lopinavir and interferon conferred clinical benefit on hospitalized patients with COVID-19. — Michele G Sullivan