FDA Grants Priority Review for Therapy for Life-threatening Hereditary Immune Disease

The FDA has accepted for priority review Regeneron’s biologics license application (BLA) for pozelimab to treat adults and children as young as 1 year of age with CHAPLE disease, an ultra-rare and life-threatening hereditary immune disease driven by an overactivation of the complement system. There are currently no approved treatments for CHAPLE. Those living with CHAPLE are unable to regulate complement activity due to mutations in the CD55 gene, a protein regulating the body’s complement system. Without proper CD55 regulation, the complement system may attack normal cells, causing damage to blood and lymph vessels along the upper digestive tract and leading to the loss of proteins and to blood cells. There are fewer than 100 patients worldwide who are known to have CHAPLE.

Pozelimab is a fully human monoclonal antibody designed to block the activity of complement factor C5, a protein involved in complement system activation. The target action date for the FDA decision is Aug. 20, 2023.

The BLA is supported by results from a phase 2/3 open-label trial that investigated the efficacy and safety of pozelimab in 10 patients aged 1 year or older. At 24 weeks, the co-primary endpoints were achieved with all patients experiencing rapid and sustained normalization of serum albumin (a disease biomarker) and improvement or no worsening of clinical symptoms. Clinical symptoms evaluated, included abdominal pain, number of bowel movements per day, and investigator-assessed facial and peripheral edema.

Analyses of secondary endpoints also demonstrated marked reductions in hospitalization days and total number of albumin transfusions, as well as clinically meaningful increases in body weight for age and stature for age. Adverse events, which occurred in 7 of 10 patients, were limited to those of mild or moderate severity with the most common being iron deficiency, pyrexia, rhinitis, urticaria and vomiting. No adverse events led to treatment discontinuation.

The FDA designated pozelimab as a treatment for rare pediatric disease and as an orphan drug in April 2020. Pozelimab was also granted fast track designation in September 2022.