Iptacopan Monotherapy Effectively Treats Persistent Anemia in PNH

Single-agent therapy with iptacopan, a first-in-class oral factor B inhibitor, improved hematologic and clinical outcomes in patients with paroxysmal nocturnal hemoglobinuria (PNH) with persistent anemia with or without prior anti-C5 therapy, according to an analysis of two phase III trials published in the New England Journal of Medicine.

Iptacopan showed superiority to anti-C5 therapy in patients with PNH who had previously received anti-C5 treatment, noted the study’s lead author, Régis Peffault de Latour, MD, of the French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria at Saint-Louis Hospital in France.

Iptacopan Effective for Anemia Treatment in PNH

Both trials in the analysis, APPLY-PNH and APPOINT-PNH, evaluated iptacopan monotherapy for 24 weeks in patients with hemoglobin levels less than 10 g/dl. In APPLY-PNH, patients on anti-C5 therapy were randomized between switching to iptacopan or remaining on their current therapy. APPOINT-PNH administered iptacopan to patients that were naïve to anti-C5 therapies and had lactate dehydrogenase (LDH) levels less than 1.5-times the upper limit of normal.

In APPLY-PNH, 51 out of 60 patients who received iptacopan achieved an increase in hemoglobin level of 2 g/dl or more from baseline and 42 achieved a hemoglobin level of at least 12 g/dl—both groups without red blood cell transfusion. Comparatively, none of the 35 patients randomized to anti-C5 therapy achieved the same endpoints. In APPOINT-PNH, 31 out of 33 patients achieved an increase in hemoglobin level of 2 g/dl or more without transfusion.

Overall, 59 out of 62 patients on iptacopan compared with 14 out of 35 on anti-C5 therapy in APPLY-PNH did not require transfusions for anemia, and no patients in APPOINT-PNH required transfusions.

Headache was the most common adverse event reported in patients treated with iptacopan.

The authors summarized that “treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range.”

Reference

Peffault de Latour R, Röth A, Kulasekararaj AG, et al. oral iptacopan monotherapy in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2024;390(11):994-1008. doi:10.1056/NEJMoa2308695