Novartis’ Iptacopan Meets 2 Endpoints for Paroxysmal Nocturnal Hemoglobinuria Treatment

The pivotal phase 3 APPLY-PNH trial (NCT04558918) met its 2 primary endpoints, showing that the investigational monotherapy iptacopan (Novartis) was superior to anti-C5 therapies, such as eculizumab and ravulizumab, in adults with paroxysmal nocturnal hemoglobinuria (PNH), who were experiencing residual anemia despite prior treatment with anti-C5 therapies.

“These positive topline phase 3 results highlight the practice-changing potential of iptacopan for patients suffering from debilitating anemia and the burden of lifelong blood transfusions as a result of PNH,” Shreeram Aradhye, MD, president of global drug development and chief medical officer at Novartis, said in a statement. “We look forward to discussing the data with regulators so we can bring this first-in-class alternative complement pathway inhibitor as the first oral monotherapy to people living with PNH.”

The topline results showed a clinically meaningful and statistically significant increase in the number of individuals who were treated with iptacopan at the 200-mg dosage twice daily, achieving hemoglobin-level increases of 2 g/dL or more from baseline without the need for blood transfusions at 24 weeks compared with anti-C5 therapies.

Additionally, investigators reported that there was a clinically meaningful and statistically significant increase in the number of individuals receiving iptacopan who achieved hemoglobin levels of 12 g/dL or more without the need for blood transfusions at 24 weeks compared with anti-C5 therapies.

The secondary endpoints include the average change in absolute reticulocyte counts, average change in hemoglobin levels, change in fatigue, average percent change in lactate dehydrogenase levels, percentage of individuals who remain free from transfusions, rate of breakthrough hemolysis, and rates of major adverse vascular events.

Investigators included 97 individuals who were randomized in an 8:5 ratio to receive either the intravenous anti-C5 therapies and oral iptacopan monotherapy twice daily , which they categorized as continuing the same regimen they were on prior to the randomization.

The company plans to present detailed results at an upcoming medical meeting and be included as part of submission to regulatory agencies in 2023.

The drug is also being studied in phase 3 trials for the atypical hemolytic uremic syndrome (NCT04889430), complement-mediated kidney diseases C3 glomerulopathy (NCT04817618), and IgA nephropathy (NCT04578834).

Additionally, there are other indications undergoing phase 2 trials, according to the statement.

PNH is a chronic, rare, and serious complement-mediated blood disorder that causes hematopoietic stem cells to produce red blood cells susceptible to premature destruction by the complement system, according to the statement.

PNH has significant unmet needs that are not addressed by available anti-C5 therapies, such as eculizumab and ravulizumab, and a large number of individuals with PNH continue to be anemic, dependent on blood transfusions, and fatigued, despite being on anti-C4 therapies, the company said.

Reference

Novartis investigational oral monotherapy iptacopan demonstrates clinically meaningful superiority over anti-C5 treatment in Phase III APPLY-PNH study. News release. Novartis. October 24, 2022. Accessed October 24, 2022. https://www.novartis.com/news/media-releases/novartis-investigational-oral-monotherapy-iptacopan-demonstrates-clinically-meaningful-superiority-over-anti-c5-treatment-phase-iii-apply-pnh-study