Novartis announced that a phase 3 trial evaluating the efficacy and safety of oral iptacopan monotherapy in complement-inhibitor-naïve adults with paroxysmal nocturnal hemoglobinuria (PNH) met its primary endpoint.

The trial assessed the proportion of participants achieving an increase in hemoglobin levels from baseline of 2 g/dL or more in the absence of red blood cell (RBC) transfusions at 24 weeks.

“We are very encouraged by the results of the complement-inhibitor-naïve data from the phase 3 APPOINT-PNH trial,” said David Soergel, MD, global head of the cardiovascular, renal and metabolism development unit of Novartis. “This second iptacopan readout for PNH underscores the robust potential for this therapy, enabling us to submit a broad regulatory package with the goal of iptacopan potentially becoming the first oral monotherapy for PNH.”

A significant proportion of patients with PNH treated with iptacopan achieved clinically meaningful hemoglobin-level increases of 2 g/dL or more from baseline without the need for red blood cell transfusions at 24 weeks, according to topline results for the study. Moreover, the safety profile of iptacopan monotherapy was consistent with previously reported data.

Recently, Novartis announced positive topline results for the pivotal phase 3 APPLY-PNH study. That study met its 2 primary endpoints and confirmed the superior performance of iptacopan over anti-C5 therapies, including eculizumab or ravulizumab, in adults with PNH experiencing residual anemia despite prior anti-C5 treatment.

Trial: Iptacopan Superior to Standard-of-Care Therapy in PNH

APPOINT-PNH is a phase 3, multinational, multicenter, open-label, single-arm study designed to evaluate the efficacy and safety of iptacopan monotherapy in adults with PNH who are naïve to complement inhibitor therapy, including anti-C5 therapies. Participants received 200 mg oral iptacopan twice daily.

In addition to the primary endpoint, investigators aim to assess the proportion of participants achieving sustained hemoglobin levels of 12 g/dL or more in the absence of RBC transfusions, transfusion avoidance, average change in hemoglobin levels and absolute reticulocyte counts, average percent change in lactate dehydrogenase levels, rate of breakthrough hemolysis, change in fatigue, and rates of major adverse vascular events.

Detailed safety data of the APPOINT-PNH study will be presented at an upcoming medical meeting and included as part of global regulatory submissions in 2023.


Novartis investigational iptacopan provides clinically meaningful increases in hemoglobin levels in complement-inhibitor-naïve patients with PNH. News release. Novartis; December 8, 2022.