investigational oral monotherapy Iptacopan demonstrates clinically meaningful superiority over anti-C5 treatment in phase III APPLY-PNH study in paroxysmal nocturnal hemoglobinuria

Detailed results will be presented at an upcoming medical meeting and included as part of global regulatory submissions in 2023.

Topline results showed a statistically significant and clinically meaningful increase in the proportion of patients treated with Iptacopan (200 mg twice daily) achieving hemoglobin-level increases of 2 g/dL or more from baseline without the need for blood transfusions at 24 weeks, compared to anti-C5 therapies, a primary endpoint of the study. Additionally, there was a statistically significant and clinically meaningful increase in the proportion of patients in the iptacopan arm achieving hemoglobin levels of 12 g/dL or more without the need for blood transfusions at 24 weeks, compared to anti-C5 therapies, also a primary endpoint of the study. Iptacopan was well tolerated with a favorable safety profile consistent with previously reported data.

Novartis is excited to continue to explore the potential of Iptacopan as the first oral monotherapy option for PNH. Iptacopan is also being studied in complement-inhibitor-naïve patients with PNH in the ongoing Phase III APPOINT-PNH trial (NCT04820530), expected to read out in the coming months.Additionally, Iptacopan is being studied in Phase III trials for the complement-mediated kidney diseases (CMKDs) C3 glomerulopathy (APPEAR-C3G [NCT04817618]), IgA nephropathy (APPLAUSE-IgAN [NCT04578834]), and atypical hemolytic uremic syndrome (APPELHUS [NCT04889430]), as well as in a number of additional indications in Phase II-

About the study: APPLY-PNH (NCT04558918) is a Phase III, randomized, multinational, multicenter, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral Iptacopan monotherapy (200 mg) for the treatment of PNH by demonstrating the superiority of iptacopan compared to anti-C5 therapies (eculizumab or ravulizumab) in adult patients presenting with residual anemia despite a stable regimen of anti-C5 treatment in the last six months prior to randomization. One primary endpoint was to assess the percentage of patients 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 week. Another primary endpoint was to assess the percentage of participants achieving sustained hemoglobin levels of 12 g/dL or more in the absence of RBC transfusions at 24 weeks.

Secondary endpoints include percentage of participants who remain free from transfusions, average change in hemoglobin levels, change in fatigue, average change in absolute reticulocyte counts, average percent change in lactate dehydrogenase (LDH) levels, rate of breakthrough hemolysis, and rates of major adverse vascular events. The trial enrolled 97 patients who were randomized in an 8:5 ratio to either twice-daily, oral iptacopan monotherapy, or intravenous anti-C5 therapies (continuing with the same regimen as they were on prior to randomization).