On August 18, 2023, the FDA approved pozelimab-bbfg (Veopoz; Regeneron Pharmaceuticals) for the treatment of patients aged ≥1 years who were diagnosed with CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE (complement hyperactivation, angiopathic thrombosis, and PLE) disease. It is unknown whether pozelimab is safe and effective in children aged <1 year.
The FDA granted pozelimab priority review and rare pediatric disease, orphan drug, and fast track designations.
Pozelimab injection is an immunoglobulin (Ig)G4 antibody, a fully human monoclonal antibody that targets complement factor C5, a protein involved in the complement system activation, and prevents diseases mediated by the complement pathway. Pozelimab is the first drug approved by the FDA for the treatment of CHAPLE disease.
CHAPLE disease is a rare and life-threatening immune disorder caused by genetic mutations of the CD55 complement regulator, which can lead to an overactivation of the complement system and result in damage to the blood and lymph vessels along the upper digestive tract and lead to a loss of circulating proteins. Worldwide, less than 100 patients have been diagnosed with CHAPLE disease. Symptoms can be life-threatening and can include abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, impaired growth, and edema, as well as severe thrombotic vascular occlusions.
“Most patients with CHAPLE disease are children who face severely debilitating symptoms and often life-threatening complications that begin in infancy,” said Michael Lenardo, MD, Chief, Molecular Development of the Immune System Section and Co-Director, Clinical Genomics Program at the National Institute of Allergy and Infectious Disease, in a press release. “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,” he noted.
The FDA approved pozelimab based on the efficacy results of a single-arm study (NCT04209634) that compared treatment outcomes and pretreatment data in 10 patients aged 3 to 19 years (median age, 8.5 years) with active CD55-deficient PLE who had hypoalbuminemia or CHAPLE disease. Active CD55-deficient PLE was defined as hypoalbuminemia (serum albumin concentration, ≤3.2 g/dL) plus ≥1 of the following signs or symptoms in the past 6 months: diarrhea, abdominal pain, peripheral edema, or facial edema. The patients received a single loading dose of pozelimab 30 mg/kg intravenously on day 1, followed 1 week later by weekly, weight-based subcutaneous doses of pozelimab.
All 10 patients achieved normalization of serum albumin and ≥3.5-g/dL serum IgG concentrations by week 12, which were maintained for at least 72 weeks. Of the 10 patients, 5 received a total of 60 albumin transfusions in the 48 weeks before treatment with pozelimab compared with only 1 patient who received 1 albumin transfusion during the 48 weeks after starting treatment with pozelimab. In addition, 9 patients were hospitalized for a total of 268 days during the 48 weeks before treatment with pozelimab compared with only 2 patients who were hospitalized for a total of 7 days after starting treatment with pozelimab, demonstrating a reduction in the number of hospitalizations and of albumin transfusions after treatment with pozelimab.
The most frequent adverse events with pozelimab occurring in ≥2 patients were upper respiratory tract infection, fractures, urticaria, and alopecia.
Pozelimab was approved with a boxed warning about the risk for serious meningococcal infections. Life-threatening and fatal meningococcal infections have occurred in patients who received complement inhibitors, and they must be recognized and treated early. Patients should complete 2 meningococcal vaccinations at least 2 weeks before receiving the first dose of pozelimab, unless the risk for delaying therapy outweighs the risk for meningococcal infection. If urgent therapy with pozelimab is needed in a patient who has not received 2 meningococcal vaccines, those vaccinations should be administered as soon as possible, in addition to antibacterial drug prophylaxis.
The recommended dosage of pozelimab is a single loading dose of a 30-mg/kg intravenous injection on day 1, followed on day 8 by a weekly maintenance dose of a 10-mg/kg subcutaneous injection, which may be increased starting by week 4 to 12 mg/kg once weekly if the patient’s response is inadequate after at least 3 weekly doses of pozelimab. The maximum maintenance dose of pozelimab is 800 mg once weekly.