Regeneron's Next-Gen C5 Complement Inhibitor Veopoz (Pozelimab) Receives FDA Approval as First Treatment for CHAPLE Disease

▎Edited by the WuXi AppTec content team

Today, Regeneron Pharmaceuticals announced that the U.S. FDA has approved the monoclonal antibody therapy Veopoz (pozelimab) for marketing. The press release noted that this isThe first FDA-approved therapy for treating adults and pediatric patients aged 1 year and older with CD55-deficient protein-losing enteropathy (CHAPLE)。

CHAPLE is an extremely rare hereditary immune disorder, with fewer than 100 known patients worldwide. Currently, there are no approved treatments for CHAPLE.CHAPLE patients are unable to regulate complement activity due to mutations in the gene encoding the CD55 protein. CD55 is a protein that regulates the human complement system. Without proper CD55 regulation, the complement system may attack normal cells, causing damage to blood and lymphatic vessels in the upper digestive tract, and leading to the loss of proteins and blood cells.In most patients, dysregulation of CD55 will trigger a series of potentially life-threatening symptoms. These adverse conditions begin in infancy and include abdominal pain, bloody diarrhea, vomiting, malnutrition, slow growth, leg swelling (edema), recurrent infections, and thrombosis.。

Pozelimab is a fully human monoclonal antibody designed to block the activity of complement factor C5 and prevent diseases mediated by the complement pathway. Structurally, pozelimab is an IgG4 antibody with high binding affinity for both wild-type and variant human complement C5 proteins.

The approval and market launch of pozelimab this time was supported by the results of a Phase 2/3 open-label clinical trial, which investigated the efficacy and safety of pozelimab in 10 CHAPLE patients aged 1 year or older. On day 1 of the trial, patients received a single dose of pozelimab at 30 mg/kg via intravenous infusion, followed by once-weekly subcutaneous injections of pozelimab based on body weight.At 24 weeks, all patients reached the co-primary endpoints, with rapid and sustained normalization of serum albumin (a disease biomarker) and improvement or no worsening of clinical symptoms.. The clinical symptoms evaluated in the study included abdominal pain, daily bowel movement frequency, and investigator-assessed facial and peripheral edema.Analysis of secondary endpoints showed a significant reduction in hospital stay duration and total albumin infusions, along with clinically meaningful increases in weight and height according to age groups.

Seven patients in the trial experienced adverse events (AEs), but all were mild or moderate AEs. The most common were iron deficiency, fever, rhinitis, urticaria, and vomiting. No AEs led to treatment discontinuation. To prevent meningococcal infection, all patients in the pozelimab trial were vaccinated against meningococcal infection prior to receiving treatment.