Tocilizumab, a treatment used for adverse events related to cancer therapy, among other indications, is being explored in a phase III trial as a treatment for adult patients hospitalized with severe COVID-19 pneumonia, according to Genentech (Roche), the manufacturer of the interleukin-6 receptor antagonist.
Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development of Genentech (Roche)
Levi Garraway, MD, PhD
Tocilizumab (Actemra), a treatment used for adverse events related to cancer therapy, among other indications, is being explored in a phase III trial as a treatment for adult patients hospitalized with severe COVID-19 pneumonia, according to Genentech (Roche), the manufacturer of the interleukin-6 receptor antagonist.1
UPDATE 3/23/2020: FDA OKs Launch of Phase III Tocilizumab Trial for COVID-19 Pneumonia
Genentech is collaborating with the Biomedical Advanced Research and Development Authority (BARDA), a part of the US Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR), to evaluate tocilizumab combined with standard of care versus placebo plus standard of care.
According to Genentech, this study is the first global trial in this setting. Enrollment is expected to start as early as April 2020, with a target accrual of 330 patients across the United States and other countries. Investigators will follow patients for 60 days after randomization and early proof of efficacy will be assessed at an interim analysis. Key study endpoints will be clinical status, mortality, mechanical ventilation, and intensive care unit variables.
"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 this disease," Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Genentech, said in a press release. “In these unprecedented times, today’s announcement is an important example of how industry and regulators can collaborate quickly to address the COVID-19 pandemic, and we will share the results as soon as possible.”
Genentech explained in the press release that there are already multiple independent clinical trials evaluating tocilizumab as a potential therapy for patients with COVID-19 pneumonia; however, none of these trials is well-controlled and there have been limited published results regarding the efficacy and safety of tocilizumab in patients with COVID-19. The company also noted that, “Actemra has been included in the 7th updated diagnosis and treatment plan for COVID-19 issued by China’s National Health Commission,” which was released on March 3, 2020.”
As the CAR T-cell therapy revolution has spread across the treatment paradigm for patients with hematologic malignancies, tocilizumab has become critical to ensuring that patients are able to receive this type of therapy. Specifically, tocilizumab is approved by the FDA for the treatment of cytokine release syndrome (CRS) that is severe or life-threatening. CRS is the most severe toxicity associated with CAR T-cell therapy. Tocilizumab is used in adults and children aged 2 years and older who have CRS caused by CAR T-cell therapy.
Tocilizumab has been a critical component to ensuring the success of several pivotal clinical trial of CAR T-cell therapy. For example, the FDA is currently reviewing a biologics license application for the anti-CD19 CAR T-cell therapy lisocabtagene maraleucel for the treatment of adult patients with relapsed/refractory large B-cell lymphoma after at least 2 prior therapies, based on data from the multicenter phase I TRANSCEND NHL 001 study.2 In this pivotal trial, the incidence of any grade CRS was 42%, which occurred at a median onset of 5 days. Nineteen percent of patients received tocilizumab to manage CRS. Nearly all cases of CRS were entirely reversible.
The FDA is also currently reviewing a biologics license application for the investigational CAR T-cell therapy KTE-X19 as a treatment for adult patients with relapsed/refractory mantle cell lymphoma. The designation is based on findings from the phase II ZUMA-2 trial, in which grade ≥3 CRS and occurred in 15% of patients and no grade 5 CRS events occurred.3 Tocilizumab was used for CRS management in 59% of patients. Overall, the median time to onset of CRS was 2 days and the median duration was 11 days. All events resolved.
Beyond CRS, tocilizumab also has FDA-approved indications for rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis.