Apellis stops COVID-19 program after missing mortality endpoint

Apellis Pharmaceuticals has stopped development of APL-9 in severe COVID-19 patients after an interim review of phase 1/2 mortality data. The review found adding the C3 therapy to standard of care had no meaningful effect on mortality, prompting Apellis to pull the plug on the program.

Massachusetts-based Apellis originally identified the pegylated synthetic cyclic peptide APL-9 as a way to control the complement system in host responses to AAV gene therapies. As evidence of the effects of the coronavirus built up early last year, Apellis posited that the mechanism of action may also help COVID-19 patients by stopping activation of part of the complement pathway and, in doing so, reduce inflammation in the lungs.

Apellis filed to test that idea in the clinic in May, leading to randomization of patients with COVID-19 and mild to moderate acute respiratory distress syndrome to receive APL-9 or placebo intravenously on top of standard of care.

The trial failed to support further development in COVID-19. Apellis is yet to share data from the trial, stating only that the interim review “found no meaningful reduction in the overall mortality rate in patients treated with APL-9 in combination with standard of care therapy compared to standard of care alone.” The efficacy part of the interim review only looked at the mortality data.

Apellis completed enrollment and last patient visit prior to the release of the interim review findings. The biotech will analyze the full data set and share the results at a scientific forum, but has already decided against further development of APL-9 in severe COVID-19.  

APL-9 was one of a number of existing clinical-phase and commercial drugs that researchers sought to repurpose for use in COVID-19 as the pandemic spread early last year. Most of the clinical trials failed but the effort yielded some successes, with dexamethasone, Eli Lilly’s baricitinib and Gilead’s remdesivir among the existing molecules to become part of the COVID-19 treatment toolkit.