FDA approves first treatment for CD55-deficient protein-losing enteropathy (CHAPLE disease)

Action

FDA has approved Veopoz (pozelimab-bbfg) injection, a complement inhibitor, for the treatment of adult and pediatric patients 1 year of age and older with CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease. Veopoz is the first FDA-approved treatment for CHAPLE disease. An initial dose of Veopoz is administered intravenously, followed by weekly injections given subcutaneously (below the skin) by a health care provider. See prescribing information for detailed dosing information.

Disease or Condition

CHAPLE—which stands for complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy—is an inherited immune disease that causes the complement system (the part of your immune system that defends the body against injury and foreign invaders like bacteria and viruses) to become overactive. It is caused by mutations of the complement regulator CD55 gene, which can lead to the complement system attacking the body’s own cells.

CHAPLE disease is a rare disease, with fewer than 100 patients diagnosed worldwide. Symptoms can include abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, impaired growth, and edema (swelling). Severe thrombotic vascular occlusions (blockage of blood vessels) can also occur among patients with CHAPLE disease, which can be life-threating.

Efficacy

The efficacy and safety of Veopoz was evaluated in a single-arm study (NCT04209634), in which patients’ outcomes were compared to pre-treatment data in patients with active CD55-deficient protein-losing enteropathy (PLE) who had hypoalbuminemia. Patients’ diagnoses were based on a clinical history of PLE symptoms and with a confirmed genotype of biallelic CD55 loss-of-function mutation. Active CD55-deficient PLE was defined as hypoalbuminemia (serum albumin concentration of ≤3.2 g/dL) with one or more of the following signs or symptoms within the last six months: diarrhea, abdominal pain, peripheral edema, or facial edema.

Patients received a single 30 mg/kg loading dose of Veopoz administered by intravenous infusion, followed by a weekly maintenance dosage, based on body weight, administered as a subcutaneous injection starting one week after the loading dose. Ten patients ranging from 3 to 19 years of age (median of 8.5 years) were assessed for efficacy. All 10 patients achieved a serum albumin concentration of at least 3.5 g/dL by week 12, which was maintained through at least 72 weeks. All 10 patients also demonstrated a reduction in the number of hospitalizations and number of albumin transfusions over the first 48 weeks of treatment as compared to the 48 weeks prior to treatment.

Safety

The most common adverse reactions to Veopoz are upper respiratory tract infections, fractures, hives, and alopecia. Veopoz has a Boxed Warning for serious meningococcal infections. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors and may become rapidly life-threatening or fatal if not recognized and treated early. Patients receiving Veopoz should complete or update meningococcal vaccination at least two weeks before treatment. Patients receiving Veopoz are at increased risk for invasive disease caused by N. meningitidis, even if they develop antibodies following vaccination. Patients are also at increased risk of other bacterial infections, particularly those caused by encapsulated bacteria (such as Streptococcus pneumoniae, Haemophilus influenzae type b (Hib) and Neisseria gonorrhoeae). Patients should receive vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), per the Advisory Committee on Immunization Practice guidelines. See full prescribing information for additional information on risks associated with Veopoz.

Designations

Veopoz received fast track, orphan drug, and rare pediatric disease designations.