DUBLIN – Genentech Inc. has succeeded where Sanofi SA and its partner Regeneron Pharmaceuticals Inc. have failed in obtaining some sort of a positive signal from a clinical trial of an interleukin-6 (IL-6) inhibitor in COVID-19. Genentech, a subsidiary of Basel, Switzerland-based Roche Holding AG, reported Sept. 18 that hospitalized patients who received Actemra/RoActemra (tocilizumab) plus standard of care were 44% less likely to require mechanical ventilation than those on standard of care only. The treatment did not improve survival, however.

In absolute terms, 12.2% of those in the active treatment arm progressed to mechanical ventilation over 28 days, as compared with 19.3% of those in the control arm. The mortality rate was actually higher in the Actemra arm (10.4%) than in the placebo arm (8.6%), but the difference was not statistically significant (p=0.5146).

Actemra also failed to attain several other key endpoints, including reducing time to hospital discharge and reducing time to clinical failure. Although it was numerically superior to placebo on both of these measures, the differences were not statistically significant. Actemra was not associated with any increase in infections or serious infections by D28. The most common side effects associated with Actemra were constipation (5.6%), anxiety (5.2%) and headache (3.2%).

The phase III Empacta study recruited 389 hospitalized patients who were not in need of mechanical ventilation or non-invasive ventilation, but who were hypoxic, with an oxygen saturation level below 94% while on ambient air. About 85% of the study participants were from ethnic groups who are usually under-represented in clinical trials but who are also particularly vulnerable to severe COVID-19 disease. The majority of participants were Hispanic; the study also recruited significant numbers of Native American and Black patients. The trial was conducted across the U.S., South Africa, Kenya, Brazil, Mexico and Peru.

Roche said it plans to share the data with the FDA and other drug regulators around the world. The data provide some evidence that Actemra may be useful. Given the trauma and long-term sequelae associated with mechanical ventilation, any reduction in use would be welcome, but it is not clear who would be likely to derive most benefit from the therapy. A recent study from The Icahn School of Medicine at Mount Sinai, N.Y., identified IL-6 as being strongly predictive of decreased survival. The study authors suggested that patients with moderate disease but high IL-6 levels could benefit from an IL-6 inhibitor, but this hypothesis has yet to be tested prospectively.

The present study is the second phase III trial of Actemra in COVID-19 that Roche has completed. In July, it reported that the Convacta trial in adult hospitalized patients with severe pneumonia failed to meet the primary endpoint of improved clinical status. It also failed to demonstrate any improvement in survival. A third phase III study, the Remdacta trial, is still recruiting. It is comparing a combination of Actemra plus the antiviral nucleotide analogue Veklury (remdesivir) with placebo plus remdesivir in hospitalized patients with severe disease.

No Comments