WHO Rolls Out Unprecedented Global Trial to Study New Drugs that Could Lower Mortality in COVID-19 Patients

The World Health Organization (WHO) has announced the next phase in its Solidarity trial for promising drugs that will roll out in 52 countries in an unprecedented global collaboration for COVID-19 R&D.

The Solidarity PLUS trial will enroll hospitalized COVID-19 patients to test three new drugs - artesunate, imatinib and infliximab - produced by Ipca Laboratories (Maharashtra, India), Novartis (Basel, Switzerland) and Johnson & Johnson (New Brunswick, N.J., USA), respectively. These therapies were selected by an independent expert panel for their potential in reducing the risk of death in hospitalized COVID-19 patients. They are already used for other indications: artesunate is used for severe malaria, imatinib for certain cancers, and infliximab for diseases of the immune system such as Crohn’s Disease and rheumatoid arthritis.

Artesunate which is used to treat malaria will be administered intravenously for seven days during the trial, using the standard dose recommended for the treatment of severe malaria. Artesunate is a derivative of artemisinin, an anti-malarial drug extracted from the herb Artemisia annua. Artemisinin and its derivatives have been extensively used in the treatment of malaria and other parasitic diseases for over 30 years, and are regarded as being very safe. The WHO COVID-19 Therapeutics Advisory Group recommended evaluating the anti-inflammatory properties of artesunate.

Imatinib which is used to treat certain cancers will be administered orally, once daily, for 14 days during the trial. The dose used is the standard maintenance dose, which is at the lower end of the dose patients with hematological malignancies are given over extended periods. Imatinib is a small molecule tyrosine kinase inhibitor, formulated as an oral chemotherapy drug used to treat certain types of cancer. Experimental and early clinical data suggest that imatinib reverses pulmonary capillary leak. A randomized clinical trial performed in the Netherlands reported that imatinib might confer clinical benefit in hospitalized COVID-19 patients, in the absence of safety issues.

Infliximab which is used to treat diseases of the immune system will be administered intravenously as a single dose. The dose used is the standard dose that patients with Crohn’s Disease are given over extended periods. Infliximab is a TNF alpha inhibitor, a chimeric monoclonal antibody that recognizes human TNF alpha. Anti-TNF biologics have been approved for treatment of certain autoimmune inflammatory conditions for more than 20 years, demonstrating favorable efficacy and safety in restricting broad spectrum inflammation, including in elderly populations who are most clinically vulnerable to COVID-19.

The Solidarity PLUS trial is a platform trial that represents the largest global collaboration among WHO Member States. It involves thousands of researchers in over 600 hospitals in 52 countries, 16 more countries than the first phase of trials. This allows the trial to assess multiple treatments at the same time using a single protocol, recruiting thousands of patients to generate robust estimates on the effect a drug may have on mortality - even moderate effects. It also allows new treatments to be added and ineffective treatments to be dropped throughout the course of the trial. Previously, four drugs were evaluated by the trial. The results showed that remdesivir, hydroxychloroquine, lopinavir and interferon had little or no effect on hospitalized patients with COVID-19. Through the Solidarity PLUS trial, researchers across the world have an opportunity to use their expertise and resources to contribute to global COVID-19 research.

“Finding more effective and accessible therapeutics for COVID-19 patients remains a critical need, and WHO is proud to lead this global effort,” said Dr. Tedros Adhanom Ghebreyesus, WHO Director-General. “I would like to thank the participating governments, pharmaceutical companies, hospitals, clinicians and patients, who have come together to do this in true global solidarity.”

Related Links:
Ipca Laboratories
Novartis
Johnson & Johnson