ERS 2022: ALERT: COVID and Interstitial Lung Diseases
In the ALERT session (Abstracts Leading to Evolution in Respiratory Medicine Trials), experts showcased important and very late-breaking clinical trial data on various novel drugs for managing respiratory diseases.
In COVID-19 patients, blocking the complement component 5a- C5a receptor (C5a-C5aR) axis may improve outcomes by limiting myeloid cell infiltration in damaged organs and preventing excessive lung inflammation and endothelialitis. Vilobelimab (VILO), an anti-C5a monoclonal antibody (mAb) that preserves the membrane attack complex (MAC), was tested for survival in critically ill COVID-19 patients in phase 3 adaptively designed multicenter, double-blind, placebo-controlled study. VILO reduced 28-day all-cause mortality compared to placebo, with a 22.7% relative mortality reduction to day 60. In severe COVID-19 pneumonia patients, the reduction in mortality by VILO with no increase in infections indicated the importance of targeting C5a while preserving MAC. Vilobelimab has a favourable safety profile in critically ill COVID-19 patients.
Oral anti-viral therapies have been licensed worldwide for COVID-19. A multicenter, open-label, randomized controlled trial was conducted to evaluate the safety and efficacy of oral favipiravir in patients hospitalized with COVID-19. A faster rate of recovery and a 66% improvement in mechanical ventilation-free survival were observed in patients receiving favipiravir. The study concluded that orally administered favipiravir has a beneficial effect on recovery, and mechanical ventilation free-survival in patients under 60 years of age, hospitalized with COVID-19.
Neutrophil serine proteases (NSPs) play a role in COVID-19 pathogenesis and are elevated in a severe and fatal infections. In a randomized, double-blind, placebo-controlled trial involving 406 hospitalized patients with COVID-19, the authors investigated whether treatment with Brensocatib, an inhibitor of dipeptidyl peptidase-1, an enzyme responsible for the activation of NSPs, would improve outcomes. The study concluded that brensocatib treatment did not improve day 29 clinical status in hospitalized patients with COVID-19.
Interferon beta (IFN-?) is essential in host defence against viruses but can be suppressed locally at the site of infection by virus or host factors. SNG001 (IFN-?-1a nebulizer solution) inhalation aims to restore lung IFN-? levels. SNG001 could become a useful treatment option for hospitalized COVID-19 patients if the encouraging signal in the relative risk of disease progression or death (approximately 30% reduction) observed in this 300 patient/arm trial was confirmed in a larger trial. However, the study did not meet the primary endpoint of hospital discharge/recovery.
A randomized, double-blinded, placebo-controlled, phase 2 study was conducted to evaluate pirfenidone's safety,tolerability, and efficacy for treating patients with rheumatoid arthritis interstitial lung disease (RA-ILD). Despite being underpowered to assess the primary endpoint, pirfenidone slowed the rate of forced vital capacity (FVC) decline over time in patients with RA-ILD.In addition, the safety of pirfenidone in patients with RA-ILD was similar to that seen in other pirfenidone trials.
Nintedanib is approved for the treatment of adult pulmonary fibrosis. There are no approved treatments for fibrosing interstitial lung disease (ILD) in children and adolescents. The InPedILD trial aimed to determine the dosing and safety of nintedanib in children and adolescents with fibrosing ILD. The InPedILD trial will provide insights into the risk-benefit ratio of nintedanib in children and adolescents with fibrosing ILD. Nintedanib has an acceptable safety and tolerability profile in children and adolescents with fibrosing ILD, and percentage predicted FVC trend over 24 weeks showed a clear improvement of using nintedanib in such patients (although the trial was not powered for this outcome)
European Respiratory Society (ERS) International Congress 2022, 3rd-6th Sept. 2022, Barcelona
