FDA Approves Regeneron’s Veopoz as the First Treatment for Children and Adults with CHAPLE Disease

Rare Daily Staff

The U.S. Food and Drug Administration has approved Regeneron’s Veopoz as the first and only treatment for adult and pediatric patients 1 year of age and older with CHAPLE disease, an ultra-rare hereditary immune disease also known as CD55-deficient protein-losing enteropathy.

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 United States.

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 Yancopoulos, 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.”

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.

Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Meningococcal infections may rapidly become life-threatening or fatal if not recognized and treated early. 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 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 reviewed under Priority Review, and the company received a Rare Pediatric Disease Priority Review voucher upon approval. Veopoz was previously granted Rare Pediatric Disease designation, Orphan Disease designation and Fast Track designation.

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

Photo: George Yancopoulos, board co-chair, president and chief scientific officer at Regeneron