Genentech finds right endpoint to show IL-6 benefit in COVID-19
Preventing mechanical ventilation may be the primary benefit of IL-6 inhibition
Genentech and Roche may have finally found an endpoint that can tease out the benefit of IL-6 inhibitors in treating COVID-19 patients.
The Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY) said Friday that the Phase III EMPACTA trial of Actemra tocilizumab met the primary endpoint by showing a 44% reduction in progression to mechanical ventilation or death vs. placebo plus standard of care in patients with COVID-19 associated pneumonia (p=0.0348).
Late-stage COVID-19 patients exhibit cytokine storm symptoms similar to those experienced by cancer patients receiving CAR T therapy, where IL-6 inhibitors such as Actemra have been shown to be effective.
But three prior Phase III trials of IL-6 inhibitors had all failed to demonstrate a clinical benefit. Each of these studies had similar primary endpoints that looked for improvements in clinical status based on a seven-category ordinal scale.
In late July, Genentech said that Actemra missed the primary endpoint of an improvement in clinical status vs. placebo in the Phase III COVACTA trial. Similarly, Kevzara sarilumab from partners Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and Sanofi (Euronext:SAN; NASDAQ:SNY) missed the primary endpoint in two Phase III trials assessing clinical improvement on a seven-category ordinal scale. One of the Kevzara trials enrolled patients who were already on mechanical ventilation (see “First Phase III Data for an IL-6 mAb in COVID-19 Disappoint”).
In EMPACTA, Actemra repeated that result once more, failing to show improvement on the seven-category scheme as a secondary endpoint. It also failed to demonstrate benefit on two other secondary endpoints, mortality and time to hospital discharge.
Where Actemra succeeded was reducing the need for mechanical ventilation, which alone can be a meaningful outcome for hospitalized patients.
The EMPACTA study is also set apart by the fact that was the first Phase III trial for COVID-19 to target enrollment of racial and ethnic minorities, which have been disproportionately affected by the pandemic. Genentech said 85% of the study’s 389 patients were from racial or ethnic minority groups, with the majority Hispanic. The study was conducted in the U.S., South Africa, Kenya, Brazil, Mexico and Peru (see Back to School 2020: “Biopharmas Must Address the Reality of Racial Disparities”).
Roche said the trial was part of the company’s Advancing Inclusive Research initiative, which aims to address barriers in clinical research for underrepresented racial and ethnic groups.
Roche said it plans to share the data with FDA and other regulators to assess the next steps.
Actemra is also being tested in the Phase III REMDACTA trial in combination with Veklury remdesivir vs. Veklury alone. The primary endpoint is an improvement in clinical status as assessed by a seven-category ordinal scale. The fraction of patients who require mechanical ventilation and the number of ventilator-free days are secondary endpoints.
IL-6 – Interleukin-6