Ultra-Rare Immune System Disease Gets First FDA-Approved Treatment

The FDA approved pozelimab (Veopoz) as the first treatment for adults and children ages 1 year and up with CD55-deficient protein-losing enteropathy.

Also known as CHAPLE (complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy) disease, CD55-deficient protein-losing enteropathy is an inherited disease marked by mutations of the complement regulator CD55 gene, which causes the complement system to attack patients' cells.

A wide range of symptoms accompany the disease, ranging from gastrointestinal effects (abdominal pain, nausea and vomiting, diarrhea) to impaired growth or peripheral or facial edema. Patients are also at risk of potentially life-threatening 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, of the National Institute of Allergy and Infectious Disease, in a press release from drugmaker Regeneron Pharmaceuticals.

Worldwide, only 100 patients have been diagnosed with the ultra-rare disease.

Approval was based on findings from a single-arm, open-label phase II/III trial that included 10 patients (range 3 to 19 years) with symptomatic CD55-deficient protein-losing enteropathy (diarrhea, abdominal pain, or edema in the prior 6 months) and hypoalbuminemia. Diagnosis was based on clinical symptoms consistent with CHAPLE disease, along with a confirmed genotype of biallelic CD55 loss-of-function mutation.

Outcomes while on the complement inhibitor pozelimab were compared against patients' pretreatment data.

"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," said Lenardo. "The approval of pozelimab is a milestone to celebrate, providing a new medicine that can help these long-suffering patients."

In the trial, all 10 patients achieved normalization (≥3.5 g/dL) of serum albumin concentrations at week 12, and this was maintained through at least 72 weeks. In the 48 weeks prior to treatment, half of the patients received 60 albumin transfusions, which dropped to one transfusion in one patient over 48 weeks of treatment. Similarly, hospitalizations dropped from a total of 268 days among nine patients to 7 days among two patients during treatment.

Pozelimab is administered by a medical provider, given as an intravenous injection (30 mg/kg loading dose) followed by weekly weight-based subcutaneous injections for maintenance (10 mg/kg). If a lack of clinical response is seen by week 3, maintenance dosing can be increased to 12 mg/kg (maximum 800 mg).

Adverse events seen in two or more patients in the pivotal trial included upper respiratory tract infection, fracture, urticaria, and alopecia.

Prescribing information for pozelimab contains a boxed warning over the risk of serious meningococcal infections that require early recognition and treatment, as complement inhibitors have been associated with life-threatening and fatal infections caused by Neisseria meningitidis.

At least 2 weeks before starting pozelimab, eligible patients should either complete or update their meningococcal vaccination, the FDA said, though vaccination does not completely eliminate the risk.

It is also advised that patients receive vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b in accordance with recommendations from the Advisory Committee on Immunization Practice, as patients may be at risk for these infections as well.

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