Vilobelimab may reduce mortality in patients with severe COVID-19 pneumonia

Treatment with vilobelimab reduced mortality at 28 to 60 days in patients with severe COVID-19 pneumonia without increasing infections, according to data presented at the European Respiratory Society International Congress.

Vilobelimab (InflaRx) is a first-in-class monoclonal antibody that targets the complement activation product C5a that preserves the membrane attack complex.

“It was already known that C5a has a strong role in this severe lung injury, and there were already investigations that blocking C5a reduces the lung injury,” Alexander P.J. Vlaar, MD, PhD, from the department of intensive care medicine at Amsterdam University Medical Center, said during a presentation.

Vlaar and colleagues first conducted an open-label, randomized, phase 2 trial of the PANAMO study in 30 patients with severe COVID-19 pneumonia who were randomly assigned vilobelimab and best supportive care or best supportive care alone. In this trial, researchers demonstrated that the primary endpoint of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2:FiO2) ratio was not different between the two groups and concluded that it was not suitable for this patient population. However, there were 50% lower mortality rates among those in the vilobelimab group vs. best supportive care group (13% vs. 27%). This led researchers to begin the phase 3 trial.

This phase 3, adaptively designed, multicenter, double-blind, placebo-controlled study included 369 critically ill patients with COVID-19 pneumonia. All patients were randomly assigned six 800 mg infusions of vilobelimab (n = 177; mean age, 56.7 years; 70.6% men) or placebo (n = 191; mean age, 55.9 years; 66.5% men) in addition to standard of care within 48 hours of intubation.

The primary outcome was 28-day all-cause mortality. Secondary outcomes included 60-day all-cause mortality, improvement in WHO Ordinal Scale at 15 and 28 days, acute kidney injury during ICU stay at 28 days, free of renal replacement therapy within 28 days and safety.

Researchers reported a 10% absolute reduction and 23.9% relative reduction in 28-day mortality. This meant one additional life was saved for every 10 patients treated with vilobelimab, according to Vlaar. These reductions continued up to day 60, with a 22.7% relative reduction in mortality, meaning one additional life was saved for every nine patients treated with vilobelimab, Vlaar said.

In a prespecified subgroup analysis of patients with high WHO Ordinal Scale of at least seven, severe acute respiratory distress syndrome or baseline renal failure, there was a relative reduction of 43% in 28-day mortality (P = .0142) and a 31.6% relative reduction at 60 days (P = .0287) in Western Europe. This equated to an additional life saved for every six patients treated with vilobelimab, according to Vlaar. Also in this analysis, researchers reported the highest impacts of anti-C5a treatments among patients with high WHO Ordinal Scale (P = .027), baseline ARDs (P = .0441) or baseline renal failure (P = .0358).

In addition, the safety of vilobelimab was favorable, Vlaar said.

“InflaRx is now discussing approval for the drug and we’re waiting for that,” Vlaar said.