COVID-19, the disease caused by the novel virus SARS-CoV-2, is a respiratory disease that is easily transmitted between people. Many people experience only mild symptoms or no symptoms at all. Mild symptoms include fever, cough, fatigue, myalgia, breathing difficulties, and loss of smell and taste. However, a significant percentage of patients develop severe pneumonia, which can progress to acute respiratory distress syndrome (ARDS) or multi-organ failure. The infection fatality rate for COVID-19 is likely around 1%, with much higher rates in older patients and patients with certain preexisting conditions.
Critical COVID-19 is characterized by inflammation and thrombosis, in addition to respiratory symptoms and damage to lung tissue. Patients show abnormalities in the coagulation system and elevated levels of proinflammatory cytokines as well as infiltration of macrophages and neutrophils in the lung. Several studies have demonstrated widespread complement activation in lungs and kidneys in humans as well as in animal models of the disease. The complement component C5a has been implicated in the pathology of COVID-19 in two ways: C5a can attract and activate neutrophils, which leads to tissue damage, and it can activate the coagulation system via its action on endothelial cells and neutrophils. Thus, C5a might have a central role in the development of ARDS as well as in vascular thrombosis (blood clots in the veins) in COVID-19.
Currently, few treatment options for critical COVID-19 exist. In addition to supportive care, dexamethasone, a corticosteroid with anti-inflammatory and immunosuppressive effects, has been shown to be beneficial in hospitalized patients who require supplemental oxygen. Further, remdesivir, a broad-spectrum antiviral, may shorten the recovery time for people with critical COVID-19.
Based on the involvement of C5a in COVID-19, InflaRx initiated a Phase II/III clinical study in March 2020. The Phase II part of the study evaluated vilobelimab treatment plus best supportive care compared to best supportive care alone for up to 28 days. The Phase II part was randomized and enrolled a total of 30 patients. The 28-day all-cause mortality rate was 13% (n = 2 out of 15) in the vilobelimab treatment arm compared to 27% (n = 4 out of 15) in the best supportive care arm. In the IFX‑1 treatment arm, fewer patients experienced renal impairment assessed by estimated glomerular filtration rates and more patients showed reversal of blood lymphocytopenia and a greater lowering of lactate dehydrogenase concentrations as a sign of reduction in tissue damage. A temporary, but statistically significant increase of D-dimer levels in the first days following vilobelimab administration was noted, as a potential signal for induction of blood clot lysis. No statistically significant group differences on the chosen primary endpoint of relative change (%) from baseline to day 5 in oxygenation index (defined as PaO2/FiO2 ratio) were detected. The Phase II results have been published in The Lancet Rheumatology .
In September 2020, InflaRx initiated the randomized, double-blinded, placebo-controlled Phase III part of the study in the Netherlands and received regulatory approval to start the trial in Germany. In October 2021, InflaRx reported that enrollment had completed in the Phase III part of the global Phase II/III trial evaluating vilobelimab in mechanically ventilated patients with COVID-19. A total of 369 patients across several countries, including in Europe, South America and other regions, were enrolled. Topline data at the 28-day mortality primary endpoint was published in Q1 2022.
In October 2021, InflaRx announced that it had received a grant of up to EUR 43.7 million from the German Ministry of Education and Research and the German Ministry of Health to support the Company’s development of vilobelimab for the treatment of critical COVID-19 patients. The initial tranche amounts to EUR 25.8 million (approximately USD 29.9 million) and is structured as reimbursement of 80% of certain pre-specified expenses related to the clinical development and manufacturing of vilobelimab. The remainder of the grant will be awarded in three additional subsequent tranches, each conditional on reaching agreed-upon development and manufacturing-related milestones for the preceding tranche and structured as reimbursement for Company expenses. Individual tranches will not be paid if the preceding milestone of a tranche is not met. Payments from this grant to the Company are expected to begin in Q4 2021.
(funding number 16LW00113)