Genentech (Roche) plans a Phase III clinical trial to assess its marketed drug Actemra (tocilizumab) as a treatment for severe cases of COVID-19 in adults. In collaboration with the Biomedical Advanced Research and Development Authority (BARDA), the prominent company initiated the COVACTA trial. Perking University First Hospital also commenced a study utilizing tocilizumab ongoing.
The U.S. Study
Genentech reported recently that it was working with the U.S. Food & Drug Administration (FDA) to initiate the randomized, double-blind, placebo-controlled Phase III clinical trial in collaboration tih BARDA as part of the U.S. Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR) to evaluate the safety and efficacy of Actemra® (tocilizumab) plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia compared to placebo plus standard of care. The primary and secondary endpoints include clinical status, mortality, mechanical ventilation and intensive care unit (ICU) variables.
Commencing in April
The first global study of tocilizumab, the industry sponsor announced the study should start in early April targeting approximately 330 patients in the United States and at other research sites around the world.
Assessing Efficacy of Actemra Fighting COVID-19
Levi Garraway, MD, PhD, chief medical office and head of Global Product Development, reported, “We are initiating a clinical trial to study Actemra for the treatment of people hospitalized with COVID-19 pneumonia, so that we can better establish the potential role for Actemra in fighting the disease.”
Evidence Thus Far
There have been several independent clinical trials, reported Genentech (Roche) in their press release, highlighting the drug has been included in the 7th updated diagnosis and treatment plan for COVID-19 issued by China’s National Health Commission (NHC) on March 3, 2020.
Presently, Peking University First Hospital is sponsoring a clinical trial targeting 150 patients in China. The purpose of this particular study is to study and evaluate the efficacy and safety of another drug, favipiravir, in combination with tocilizumab for the treatment of coronavirus disease 2019. The study has three arms including a tocilizumab group alone. This study started on March 8, 2020 and will end in May, 2020. The study has signed up 11 clinical investigational sites (all hospitals or health centers) and is led by principal investigator Guiqiang Wang with Peking University First Hospital.
What is tocilizumab?
Also know as Actemra, the immunosuppressive drug is used mostly for the treatment of rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis, a severe form of arthritis in children. A humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)—which is a cytokine that plays an important role in immune response and is implicated in pathogenesis of many diseases—from autoimmune diseases, multiple myeloma and prostate cancer, it originated from research and development in Hoffman-La Roche and Chugai.
The company’s formal description (under title of Actemra):
Actemra was the first humanized interleukin-6 (IL-6) receptor antagonist approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have used one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), that did not provide enough relief. The extensive Actemra RA IV clinical development program included five Phase III clinical studies and enrolled more than 4,000 people with RA in 41 countries. The Actemra RA subcutaneous clinical development program included two Phase III clinical studies and enrolled more than 1,800 people with RA in 33 countries. Actemra subcutaneous injection is also approved for the treatment of adult patients with giant cell arteritis (GCA) and for patients two years of age and older with active polyarticular juvenile idiopathic arthritis (PJIA) or active systemic juvenile idiopathic arthritis (SJIA). In addition, Actemra is also approved in the IV formulation for patients two years of age and older with active PJIA, SJIA or CAR T cell-induced cytokine release syndrome (CRS). Actemra is not approved for subcutaneous use in people with CRS. It is not known if Actemra is safe and effective in children with PJIA, SJIA or CRS under two years of age or in children with conditions other than PJIA, SJIA or CRS.
Of note, upper respiratory infection (over 10% of patients) is the number one observed adverse event. This could introduce complications given the correlation of severe COVID-19 cases and upper respiratory infections. See the FDA label for all of the safety concerns associated with this powerful immunosuppressive.
Interleukin 6 and its receptor were actually discovered and cloned by activities as Osaka University in Japan in the 1980s by Tadamitsu Kishimoto. By 1997, Chugai Pharmaceuticals commenced clinical development of the drug for the treatment of RA. The company commenced clinical trials targeting Castleman’s disease and systemic juvenile idiopathic arthritis in 2001 and 2002. Based on licensing agreement, Hoffman-La Roche co-developed the drug by 2003.
Drugs.com includes an organized approval history of the drug.
Levi Garraway, MD, PhD, chief medical office and head of Global Product Development