Novartis oral blood disorder drug bests injectable rivals in trial

Novartis revealed that its phase 3 trial met both primary endpoints, showing investigational oral monotherapy iptacopan was superior to AstraZeneca/Alexion’s  currently marketed anti-C5 antibodies Soliris (eculizumab) and Ultomiris (ravulizumab) in adults with a rare chronic blood disorder.

The APPLY-PNH open-label trial evaluated the efficacy and safety of twice-daily, oral iptacopan for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare, chronic and serious blood disorder often diagnosed in people between 30-40 years old by demonstrating the superiority of iptacopan compared to rival anti-C5 therapies in adult patients presenting with residual anemia despite a stable regimen of anti-C5 treatment in the last six months.

Topline results showed a statistically significant and clinically meaningful increase in the proportion of patients treated with iptacopan 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.

According to Novartis, PNH has a significant unmet need not addressed by anti-C5 therapies: despite treatment with anti-C5s, a large proportion of people with PNH remain anemic, fatigued and dependent on blood transfusions. Both marketed injectable anti-C5 therapies — Soliris and its successor, Ultomoris — are AstraZeneca blockbusters, snapped up in the drugmaker's $39 billion rare disease buyout of Alexion Pharmaceuticals in late 2020.

Novartis says it will soon begin the discussion with regulators in order to bring iptacopan — also being studied in  kidney diseases — to patients.