Does vilobelimab reduce mortality in severe COVID-19? 

Vilobelimab may reduce mortality in patients with severe COVID-19 pneumonia, the phase 3 PANAMO trial showed. Western-European patients in particular appeared to benefit from the intervention. Since vilobelimab displayed an acceptable safety profile in this population, the developers aim to discuss the results with the regulatory authorities.

Complement activation (C5a) has been shown to play an important role in severe COVID-19 [1] and vilobelimab is a first-in-class anti-C5a monoclonal antibody that leaves the membrane attack complex (MAC) intact. Since it has been shown that C5a levels are high in patients with severe COVID-19 and related to disease severity [2], 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 study [3], the PANAMO phase 3 study (NCT04333420) was initiated [4]. 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.

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%; see Figure). However, this relative risk reduction of 23.9% was not statistically significant following site-stratified Cox regression (P=0.094), which was the approach recommended by the FDA. In Western-European participants receiving vilobelimab, the observed relative risk reduction for all-cause mortality was 43.0% compared with placebo. In other words, 1 additional life was saved for every 6 participants if they received vilobelimab. Furthermore, participants with more severe disease appeared to benefit more from treatment with vilobelimab than those with less severe disease.

Figure: 28-day mortality rate of vilobelimab- versus placebo-treated COVID-19 patients [4]



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 aims to present the results to the regulatory authorities.”

1. Java A, et al. JCI Insight. 2020;5(15):e140711.
2. Carvelli J, et al. Nature. 2020;588:146‒150.
3. Vlaar APJ, et al. Lancet Rheumatol. 2020;2(12):e764‒e773.
4. Vlaar APJ, et al. Phase 3 RCT of C5a-Specific Vilobelimab in Severe COVID-19 Pneumonia. ALERT 3, RCT2881, ERS International Congress 2022, Barcelona, Spain, 4–6 September.

Posted on 30 October 2022