The phase 2B study, APPULSE (NCT05630001), is set to evaluate the efficacy and safety of switching from standard of care anti-C5 monoclonal antibody therapy to iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria (PNH) who have a hemoglobin level equal to or greater than 10 g/dL.

“PNH patients who have a complete (transfusion independence and no anemia [Hb >12 g/dL]) or good (transfusion independence and mild anemia [Hb 10-12 g/dL]) response to eculizumab…can still have ongoing low-level extravascular hemolysis and are at risk of breakthrough hemolysis,” the study’s authors explained in an abstract released at the European Hematology Association Open Access Library.

Enrolled patients will receive iptacopan monotherapy at a dose of 200 mg twice daily for 24 weeks. The primary outcome measure is change from baseline in hemoglobin levels to demonstrate the noninferiority of iptacopan after switching from standard of care as assessed between days 126 and 168.

The noninferiority of iptacopan will be demonstrated if the lower boundary of the 95% confidence interval (CI) is superior to −1 g/dL.

Read more about PNH therapies

If the primary objective is met, the superiority of iptacopan will be further investigated by comparing the lower boundary of the 95% CI of change from baseline in hemoglobin to 0 g/dL.

Investigators will also assess the percentage of hematological responders to iptacopan treatment, change from baseline in absolute reticulocyte count levels, percentage change from baseline in lactate dehydrogenase levels, changes in treatment satisfaction and fatigue, and rates of breakthrough hemolysis and major adverse vascular events.

APPULSE-PNH will enroll approximately 50 adults with a confirmed diagnosis of PNH who are under a stable regimen of anti-C5 antibody treatment (eculizumab or ravulizumab) for at least 6 months prior to screening and have a mean hemoglobin level of 10 g/dL or greater.

In addition, participants must be vaccinated against Neisseria meningitidis and Streptococcus pneumoniae infection before starting iptacopan treatment. Vaccination against Haemophilus influenzae infections is also recommended.

Exclusion criteria include red blood cell transfusion in the 6 months prior to or during screening, history of hematopoietic stem cell or any solid organ transplantation, known or suspected hereditary complement deficiency, active systemic bacterial, viral, or fungal infection within 14 days prior to iptacopan administration, human immunodeficiency virus infection, history of recurrent invasive infections caused by encapsulated organisms, history of cancer within the past 5 years, and unstable medical conditions.

APPULSE results will add to those of the randomized phase 3 APPLY-PNH trial enrolling patients with PNH whose hemoglobin level was lower than 10 g/dL despite treatment with eculizumab or ravulizumab.


Risitano AM, Araten DJ, Kuter D, et al. APPULSE-PNH: a phase IIIB trial to evaluate the efficacy and safety of switching to optacopan in patients with paroxysomal noctural hemoglobinuria (PNH) on anti-C5 therapy with hemoglobin >10g/dL. European Hematology Association Open Access Library. Published online May 11, 2023.