FDA approves iptacopan as the first oral monotherapy for adults with PNH

The U.S. Food and Drug Administration (FDA) has approved iptacopan (Fabhalta; Novartis) as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH)1.

The FDA has approved iptacopan based on the successful outcomes of the Phase 3 APPLY-PNH trial, where it demonstrated superior efficacy in improving hemoglobin levels without the need for red blood cell transfusions compared to patients continuing anti-C5 treatments. Additionally, support from the Phase 3 APPOINT-PNH study further reinforced the approval, particularly in complement inhibitor-naïve patients. Notable findings include a significant percentage of iptacopan-treated patients achieving sustained increases in hemoglobin levels, particularly in those with prior anti-C5 experience, and a substantial transfusion avoidance rate compared to patients on anti-C5 treatments.

The most frequently reported adverse reactions (ARs) (≥10%) with iptacopan compared with anti-C5s included headache (19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection (11% vs 11%), nausea (10% vs 3%), and viral infection (10% vs 31%). Serious ARs were reported in 3% of PNH patients receiving iptacopan, involving pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, common ARs (≥10%) included headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious ARs were observed in 5% of PNH patients receiving iptacopan, with events such as COVID-19 and bacterial pneumonia. Iptacopan carries the risk of serious infections caused by encapsulated bacteria and is subject to a Risk Evaluation and Mitigation Strategy mandating vaccinations for encapsulated bacteria.

Read the full press release here.