Apellis Initiates Study of APL-9 in Patients with Severe COVID-19

Apellis Pharmaceuticals announced the company has initiated a Phase 1/2 clinical study of APL-9, an investigational C3 inhibitor designed for acute interventions, in COVID-19 patients with respiratory failure including acute respiratory distress syndrome (ARDS). ARDS is a life-threatening form of lung failure that involves overactivation of complement, a part of the body’s immune system.

In COVID-19, complement activation has also been found to be strongly associated with organ failure and thrombotic events, which involve the abnormal formation of blood clots and are an emerging cause of mortality in COVID-19 patients. Apellis initiated the Phase 1/2 study following preliminary results from its ongoing, non-interventional study in patients with ARDS secondary to COVID-19, which showed a substantial increase in the activation of the complement cascade.

The randomized, multi-center, controlled Phase 1/2 study is expected to enroll 66 hospitalized patients with COVID-19 and respiratory failure who require oxygen supplementation or mechanical ventilation. The primary objective of the study is to assess the safety of APL-9 as an add-on to the current standard of care. Secondary objectives include evaluating length of stay in the hospital, overall survival, time on oxygen therapy or mechanical ventilation, and markers of complement activation, organ failure, and coagulation (blood clotting). Apellis initiated the study upon clearance by the U.S. Food and Drug Administration (FDA), which expedited the review of the investigational new drug application for APL-9 in COVID-19. 

“ARDS and harmful blood clots are associated with mortality in COVID-19, and we believe that dysregulation of complement plays a key role in both of these conditions,” said Lukas Scheibler, Ph.D., Chief Innovation Officer at Apellis. “We look forward to evaluating the potential of APL-9 to improve clinical outcomes in COVID-19 patients by controlling complement centrally, at the level of C3.”

APL-9 is an investigational drug designed to control the complement cascade centrally at C3 and may have the potential to treat a range of diseases caused by excessive or uncontrolled activation of complement. APL-9 is a second-generation C3 inhibitor that leverages the same mechanism of action as Apellis’ lead compound, pegcetacoplan (APL-2), but has a lower molecular weight and shorter half-life. APL-9 is designed to be intravenously administered for acute use.