FDA Approves First Oral Monotherapy for Adults With PNH

The Food and Drug Administration on Tuesday approved iptacopan (Fabhalta, Novartis) as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare complement-mediated blood disorder.

Patients with PNH have an acquired mutation in the hematopoietic stem cells that causes them to produce RBCs that are susceptible to hemolysis, which can increase the risk for anemia, thrombosis, fatigue and other debilitating symptoms. Despite anti-C5 therapies, many people with PNH remain anemic, fatigued and dependent on blood transfusions.

Iptacopan is an oral Factor B inhibitor that acts proximally in the alternative complement pathway of the immune system to control RBC destruction within and outside the blood vessels.

FDA based its approval on findings from the phase III APPLY-PNH trial (in PNH patients with residual anemia despite prior anti-C5 treatment) and phase III APPOINT-PNH trial (in complement inhibitor-naïve patients). In the APPLY-PNH trial, patients who switched to iptacopan demonstrated superiority in hemoglobin improvement in the absence of RBC transfusions and transfusion avoidance rate compared with patients who stayed on anti-C5 treatments.

Common adverse reactions included headaches, infections, diarrhea, and abdominal pain. Iptacopan may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria.