Date: 21-Sep-2020

Roches Phase III EMPACTA Study Of Actemra/RoActemra In Hospitalised Patients With COVID-19 Associated Pneumonia Meets Primary Endpoint

Roche announced that the phase III EMPACTA study met its primary endpoint, showing that patients with COVID-19 associated pneumonia who received Actemra/RoActemra (tocilizumab) plus standard of care were 44% less likely to progress to mechanical ventilation or death compared to patients who received placebo plus standard of care (log-rank p-value = 0.0348; HR [95% CI] = 0.56 [0.32, 0.97]). The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the Actemra/RoActemra arm versus 19.3% in the placebo arm. The EMPACTA study did not identify any new safety signals for Actemra/RoActemra.

“The EMPACTA trial demonstrated that Actemra/RoActemra can reduce the need for mechanical ventilation in patients with COVID-19 associated pneumonia, an important outcome in this serious disease,” said Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development. “We plan to share this important data with the US Food and Drug Administration (FDA) and other health authorities around the world.”

The study is the first global, phase III COVID-19 clinical trial to primarily enrol patient populations that are often underrepresented in clinical studies and have been disproportionately affected by the COVID-19 pandemic. Approximately 85% of the 389 patients were from minority racial and ethnic groups. The majority of patients were Hispanic, with significant representation of Native American and Black populations. The trial was conducted in the United States, South Africa, Kenya, Brazil, Mexico and Peru.

“We have been striving to improve inclusion and diversity in our trials,” said Jamie Freedman, M.D., Ph.D., head of US Medical Affairs. “During the COVID-19 pandemic, we saw how high the stakes were for many communities of colour and made diversity the centerpiece of this trial.”

Patients with COVID-19 associated pneumonia who received Actemra/RoActemra plus standard of care were 44% less likely to progress to mechanical ventilation or death compared to patients who received placebo plus standard of care (log-rank p-value = 0.0348; HR [95% CI] = 0.56 [0.32, 0.97]). The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the Actemra/RoActemra arm versus 19.3% in the placebo arm.

There was no statistical difference in mortality between patients who received Actemra or placebo by day 28 (Actemra = 10.4%; PBO = 8.6%, p-value = 0.5146, Difference [95% CI]: 2.0% [-5.2%, 7.8%].

At day 28, incidence of infections was 10% and 11% in the Actemra/RoActemra and placebo arms, respectively, and the incidence of serious infections was 5.0% and 6.3% in the Actemra/RoActemra and placebo arms, respectively. The most common adverse events in patients who received Actemra/RoActemra were constipation (5.6%), anxiety (5.2%), and headache (3.2%). The EMPACTA study did not identify any new safety signals for Actemra/RoActemra.

Actemra/RoActemra is currently being investigated as a potential treatment for COVID-19 associated pneumonia, including in combination with an antiviral in the phase III REMDACTA clinical trial. Results from the phase III COVACTA trial in patients with severe COVID-19 associated pneumonia were released in July. In addition, there are a number of independent trials of Actemra/RoActemra in this setting. Actemra/RoActemra has not been approved by any health authority for COVID-19 associated pneumonia.

EMPACTA (Evaluating Minority Patients with Actemra) is a Phase III, randomised, double-blind, placebo-controlled multicenter study (EMPACTA, NCT04372186) to evaluate the efficacy and safety of Actemra in the treatment of hospitalised COVID-19 associated pneumonia among patients that are often underrepresented in clinical trials.

The trial enrolled hospitalised patients older than 18 years with confirmed SARS-CoV-2 (COVID-19) infection with SpO2 <94% while on ambient air who did not require noninvasive or invasive mechanical ventilation. The primary endpoint is the cumulative proportion of participants dying or requiring mechanical ventilation by Day 28. Secondary objectives include: time to clinical failure, defined as the time to death, mechanical ventilation, ICU admission, or withdrawal (whichever occurs first); mortality rate by Day 28; and time to hospital discharge or “ready for discharge.”

The study enrolled 389 patients in the United States, South Africa, Kenya, Brazil, Mexico and Peru.

REMDACTA Trial is a two-armed global phase III, randomised, double-blind, multi-centre study (REMDACTA, NCT04409262) to evaluate the efficacy and safety of Actemra/RoActemra plus remdesivir, versus placebo plus remdesivir in hospitalised patients with severe COVID-19 associated pneumonia receiving standard of care. The REMDACTA trial is being conducted in collaboration with Gilead Sciences, Inc. The primary endpoint of the study is clinical status as measured by a 7-Category Ordinal Scale by Day 28. Key secondary endpoints include mortality, mechanical ventilation, and intensive care variables. Patients will be followed for 60 days post-randomisation.

Actemra/RoActemra was the first approved anti-IL-6 receptor biologic available in both intravenous (IV) and subcutaneous (SC) formulations for the treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA). Actemra/RoActemra can be used alone or with methotrexate (MTX) in adult RA patients who are intolerant to, or have failed to respond to, other disease-modifying anti-rheumatic drugs (DMARDs).

In Europe, RoActemra IV and SC are also approved for use in adult patients with severe, active and progressive RA who previously have not been treated with MTX. Actemra/RoActemra IV and SC are approved globally for polyarticular juvenile idiopathic arthritis (pJIA) and in the US and Europe for systemic juvenile idiopathic arthritis (sJIA) in children two years of age and older.