Does vilobelimab reduce mortality in severe COVID-19?
Since vilobelimab displayed an acceptable safety profile in this population, the developers aim to discuss the results with the regulatory authorities.
368 critically ill, intubated patients were randomised for the study
Complement activation (C5a) has been shown to play an important role in severe COVID-19 and vilobelimab is a first-in-class anti-C5a monoclonal antibody that leaves the membrane attach complex (MAC) intact1. Since it has been shown that C5a levels are high in patients with severe COVID-19 and related to disease severity2, Prof. Alexander Vlaar (Amsterdam UMC, the Netherlands) and co-investigators deemed it reasonable to assess C5a inhibition in patients with severe COVID-19.
After the successful results of the PANAMO phase 2 study3, the PANAMO phase 3 study (NCT04333420) was initiated4. This study randomised 368 critically ill, intubated patients with COVID-19 1:1 to vilobelimab plus standard-of-care or to placebo plus standard of care. All-cause mortality after 28 days was the primary outcome.
More severe cases seem to benefit more from treatment than less ones
The results displayed a trend towards a reduced risk of all-cause mortality in the vilobelimab arm compared with the placebo arm (31.7% vs 41.6%). However, this relative risk reduction of 23.9% was not statistically significant following site-stratified Cox regression (P=0.094), the approach that was recommended by the FDA. In Western European patients receiving vilobelimab, the observed relative risk reduction for all-cause mortality was 43.0% compared with placebo. In other words, one additional life was saved for every 6 patients if they received vilobelimab. Furthermore, patients with more severe disease appeared to benefit more from treatment with vilobelimab than those with less severe disease.
In terms of safety, an acceptable safety profile of vilobelimab was reported. The rate of infections and infestations was 62.9% in the intervention arm and 59.3% in the placebo arm.
“A clinically meaningful, but non-significant, benefit was observed for treatment with vilobelimab in this critically ill population,” said Prof. Vlaar. “The developer InflaRx aims to present the results to the regulatory authorities.”