Monoclonal Antibody Reduces Mortality for SARS-CoV-2-Induced Acute Respiratory Distress Syndrome
InflaRx CEO Niels Riedemann, MD, offers insights on his company’s monoclonal antibody, which demonstrated a nearly 24% reduction in 28 day all-cause mortality.
SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) is a severe lung condition that causes fluid to build up in the lungs leading to difficulty breathing, shortness of breath, confusion, and dizziness, and patients can decompensate into complications such as blood clots and infections.1,2 About 25% to 40% of people with ARDS do not survive, even with treatment, which primarily focuses on supportive care, including oxygen therapy with mechanical ventilation, careful fluid management, and addressing underlying inflammatory processes through medications like corticosteroids.1,2
The severity of this condition combined with limited treatment options demonstrates a need for more therapeutics. A monoclonal antibody, vilobelimab (Gohibic), developed by a German company, InflaRx, is an investigational therapy being studied for the condition. Vilobelimab is a first-in-class monoclonal anti-human complement factor C5a antibody, which blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, vilobelimab leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism of the innate immune system, which is not the case for molecules blocking C5.3
“This factor, complement C5A, we are blocking and binding that. Our antibody specifically makes sure that this booster is kept under control,” said InflaRx CEO Niels Riedemann, MD.
Nearly 2 years ago, vilobelimab received an Emergency Use Authorization from the FDA for the treatment of COVID-19 in hospitalized adults when initiated within 48 hours of receiving invasive mechanical ventilation (IMV) with or without extracorporeal membrane oxygenation (ECMO). And just last month, the European Commission (EC) granted marketing authorization for a similar indication. Vilobelimab is the first and only treatment approved in the European Union for the treatment of SARS-CoV-2-induced ARDS.
Phase 3 Trial Parameters and Results
The PANAMO phase 3 trial was a randomized, placebo-controlled study that examined vilobelimab in critically ill COVID‑19 patients. This was a multicenter study across Europe, Asia, Africa, and the Americas. Participants included patients 18 years or older who were receiving invasive mechanical ventilation, but not more than 48 hours after intubation at time of first infusion, and had a PaO2/FiO2 ratio of 60–200 mm Hg, and a confirmed COVID-19 with any variant in the past 14 days were eligible for this study.4
Study participants were randomized, to receive standard of care and vilobelimab at a dose of 800 mg intravenously for a maximum of 6 doses (days 1, 2, 4, 8, 15, and 22) or standard of care and a matching placebo using permuted block randomization.4
“They showed a 23.9% relative reduction in 28 day all-cause mortality….We also looked at other endpoints, particularly 60 day mortality, where we saw a very similar signal,” Riedemann said. With other endpoints, they also showed a reduction in the need for renal replacement therapy.
Riedemann says clinicians should look at the prescriber site for more information on vilobelimab’s safety and efficacy.
This is the first in a 2-part segment. In the next segment, Riedemann discusses a rare statistical error that cost them almost 17% in outcome data.
