US FDA begins Priority Review of Regeneron’s pozelimab for treating ultra-rare immune disease

CHAPLE is caused by a mutation to a gene encoding CD55, a protein regulating the immune system’s first line of defence called the complement system. This leads the complement system to attack healthy tissue with symptoms including abdominal pain, vomiting, malnutrition and slow growth. The disease, which lacks approved treatments, manifests in infancy and affects fewer than 100 patients worldwide.

To clamp down on the immune disease, pozelimab blocks C5, a protein that activates the complement system. The monoclonal antibody is produced using mice that are genetically engineered to produce human antibodies.

To back up its market approval application, Regeneron included results from a phase 2/3 open-label trial of subcutaneous doses of pozelimab in pediatric patients with CHAPLE. By the 24-week time point, all 10 patients in the trial had restored levels of serum albumin, which is a biomarker of the disease, and their symptoms didn’t get worse. Additionally, the patients were hospitalized less and needed fewer albumin transfusions. 

With a Priority Review in hand from the FDA, Regeneron can expect a regulatory decision within 6 months of handing in the application, rather than 10 months in a standard review process. Pozelimab was also granted Orphan Drug Designation by the FDA in 2020 and Fast Track designation in 2022. This means that the company has development incentives for pozelimab such as exemption from user fees and eligibility for accelerated approval.

Another C5 blocker that has been tested​​ for the treatment of CHAPLE is eculizumab (Soliris), which is approved for the treatment of aroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis and neuromyelitis optica. The drug is administered to patients intravenously in the clinic, which can be more disruptive to patients’ lives than subcutaneous injections of pozelimab.

C5 inhibition comes with risks, as it can leave patients more vulnerable to meningococcal infections. For that reason, vaccinations for these infections are recommended at least 2 weeks before treatment with C5 inhibitors; this is what Regeneron did with its own pozelimab trial.

In addition to CHAPLE, Regeneron is testing pozelimab for the treatment of more common diseases such as paroxysmal nocturnal hemoglobinuria and myasthenia gravis. The antibody is also being tested in combination with Alnylam’s C5-blocking RNA interference drug cemdisiran.

Earlier in February, Regeneron also had regulatory success in a different pediatric program. Its approved drug aflibercept (Eylea) became the first drug treatment for retinopathy of prematurity (ROP) in preterm infants.