Pozelimab (C5 Antibody) BLA for Treatment of Children and Adults with Ultra-rare CHAPLE Disease Accepted for FDA Priority Review

Regeneron Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for pozelimab as a treatment for adults and children as young as 1 year of age with CHAPLE disease (also known as CD55 deficiency with Hyperactivation of complement, Angiopathic thrombosis and Protein Losing Enteropathy or CD55-deficient protein-losing enteropathy). There are currently no approved treatments for CHAPLE, an ultra-rare and life-threatening hereditary immune disease driven by an overactivation of the complement system. Pozelimab is an investigational 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 August 20, 2023.

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 which is a mechanism for destroying microbes. 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. In most patients, this process results in a range of potentially life-threatening symptoms beginning in infancy, including abdominal pain, bloody diarrhea, vomiting, malnutrition, slow growth, swelling in the legs (edema), recurrent infections, and blood clots. There are fewer than 100 patients worldwide who are known to have CHAPLE.

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. Patients were given a single loading dose of pozelimab 30 mg/kg intravenously on day 1, followed by subcutaneous weekly weight-based doses of pozelimab. At 24 weeks, the co-primary endpoints were achieved with 100% of 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 (AEs), 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 (n=2 each). No AEs led to treatment discontinuation.

Life-threatening meningococcal infections have occurred in patients treated with complement protein C5 inhibitors and may become rapidly life-threatening or fatal if not recognized and treated early. Recommended guidance indicates patients with complement deficiencies should be vaccinated at least 2 weeks prior to receiving a C5 inhibitor. Vaccination reduces, but does not eliminate, the risk of meningococcal infections. All patients in the pozelimab trial received vaccination for meningococcal infection prior to treatment with pozelimab.

The FDA designated pozelimab for treatment of CHAPLE as a drug for a “rare pediatric disease” in April 2020, with the opportunity for Regeneron to receive a rare pediatric disease priority review voucher should pozelimab be approved for CHAPLE. Orphan Drug Designation was granted at the same time, which is given to investigational medicines intended for the treatment of rare diseases that affect fewer than 200,000 people in the U.S. Pozelimab was also granted Fast Track designation in September 2022, which is designed to expedite the FDA’s review of innovative new drugs that demonstrate the potential to address an unmet medical need. Pozelimab is currently under clinical development for CHAPLE, and its safety and efficacy have not been evaluated by any regulatory authority.