FDA approves pozelimab as first treatment for adults and children with CHAPLE disease

The US Food and Drug Administration has approved pozelimab (Veopoz)as the first treatment for adults and children ages 1 year and up CHAPLE disease.

Also known as CD55-deficient protein-losing enteropathy it is an inherited disease marked by mutations of the complement regulator CD55 gene, which causes the complement system to attack patients' cells.

With the approval of Veopoz, the pre-approval inspection issues related to the aflibercept 8 mg BLA have been addressed. FDA action on the aflibercept 8 mg BLA is expected in the next few weeks.

“Most patients with CHAPLE disease are children who face severely debilitating symptoms and often life-threatening complications that begin in infancy,” said Michael Lenardo, M.D., Chief, Molecular Development of the Immune System Section; Co-Director, Clinical Genomics Program, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH). “As an investigator in this pivotal trial and one of the discoverers of this disease, I saw first-hand the transformational clinical improvement that pozelimab achieves in those suffering from CHAPLE. The approval of pozelimab is a milestone to celebrate, providing a new medicine that can help these long-suffering patients.”

CHAPLE is an ultra-rare and life-threatening hereditary immune disease driven by an overactivation of the complement system. In healthy individuals, the complement system is a mechanism for destroying microbes. However, those living with CHAPLE are unable to regulate complement activity due to mutations in their CD55 gene. 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 circulating proteins. There are fewer than 10 patients with CHAPLE disease identified in the U.S.

Veopoz, a fully human monoclonal antibody, is designed to target complement factor C5, a protein involved in complement system activation.

“As the first-ever treatment for CHAPLE, Veopoz is a testament to our commitment to uncovering genetic insights and applying them to the development of effective treatments for patients in need-regardless of the prevalence of their disease,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron. “Beyond CHAPLE, we believe Veopoz has promise in a variety of complement-mediated diseases and are driving forward several clinical programs to explore its broader potential.”

Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Meningococcal infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update meningococcal vaccination at least two weeks prior to administering the first dose of Veopoz, unless the risks of delaying therapy outweigh the risks of developing meningococcal infection. If urgent therapy is indicated in a patient who is not up-to-date with both meningococcal vaccines according to Advisory Committee on Immunization Practices (ACIP) recommendations, administer meningococcal vaccines as soon as possible and provide the patient with antibacterial drug prophylaxis. Vaccination reduces, but does not eliminate, the risk of meningococcal infections.

Veopoz was previously granted Rare Pediatric Disease designation, Orphan Disease designation and Fast Track designation.

About the Pivotal CHAPLE Trial

The FDA approval is based on results from a Phase 2/3 open-label trial that investigated the efficacy and safety of pozelimab in 10 patients aged 3 to 19 (median of 8.5 years). 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.

All ten patients achieved normalization of serum albumin and serum IgG concentrations by week 12 and maintained these concentrations through at least 72 weeks of treatment. Five of the 10 patients received a total of 60 albumin transfusions in the 48 weeks prior to treatment. In the 48 weeks after starting treatment, one patient received one albumin transfusion. Nine of the 10 patients were hospitalized for a total of 268 days in the 48 weeks prior to treatment. In the 48 weeks after starting treatment, two patients were hospitalized for a total of 7 days.

The most common adverse reactions occurring in two or more patients included upper respiratory tract infection, fracture, urticaria, and alopecia.

About Veopoz

Veopoz was invented using Regeneron’s proprietary VelocImmune® technology and is a fully human, monoclonal antibody designed to block the activity of complement factor C5 and prevent diseases mediated by the complement pathway. It is an IgG4 antibody that binds with high affinity to wild-type and variant human C5.

As part of its ongoing development program, Veopoz is also being evaluated in combination with Alnylam’s cemdisiran (siRNAi C5 inhibitor) as an investigational combination therapy for the treatment of other complement-mediated disorders including paroxysmal nocturnal hemoglobinuria (PNH) and myasthenia gravis (MG). This combination is currently under clinical development, and its safety and efficacy have not been evaluated by any regulatory authority.