Novartis’ iptacopan shows promise as rare blood disease treatment in phase 3 study

Novartis has announced positive topline results from a phase 3 trial in which its investigational oral monotherapy iptacopan demonstrated 'clinically meaningful superiority' over anti-C5 therapies (eculizumab or ravulizumab) in adults with paroxysmal nocturnal haemoglobinuria (PNH) experiencing residual anaemia despite prior treatment with anti-C5s.

PNH is a rare, chronic and life-threatening blood disease, with around one to two people per million worldwide newly diagnosed each year.

Those with the disease have an acquired mutation in some of their haematopoietic stem cells that causes them to produce red blood cells susceptible to premature destruction by the complement system, which can cause anaemia, thrombosis, fatigue and other debilitating symptoms that can impact quality of life.

The disease has a significant unmet need not addressed by anti-C5 therapies, Novartis reports, and despite treatment with anti-C5s, a large proportion of people with PNH remain anaemic, fatigued and dependent on blood transfusions.

Iptacopan acts upstream of the C5 terminal pathway, preventing both intravascular and extravascular haemolysis in PNH, meaning iptacopan may have a therapeutic advantage over anti-C5 therapies by targeting a key part of the biology responsible for PNH while offering an oral monotherapy option.

Topline results from the phase 3 APPLY-PNH trial, in which 97 patients were enrolled, showed a statistically significant and clinically meaningful increase in the proportion of patients treated with a 200mg dose of iptacopan twice daily achieving haemoglobin-level increases of 2g/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.

There was also a statistically significant and clinically meaningful increase in the proportion of patients in the iptacopan arm achieving haemoglobin levels of 12g/dL or more without the need for blood transfusions at 24 weeks, compared to anti-C5 therapies, another primary endpoint of the study.

Detailed results will be presented at an upcoming medical meeting and included as part of global regulatory submissions in 2023, the company said in a statement.

“These positive topline phase 3 results highlight the practice-changing potential of iptacopan for patients suffering from debilitating anaemia and the burden of lifelong blood transfusions as a result of PNH,” said Shreeram Aradhye, president, global drug development and chief medical officer, Novartis.

“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,” Aradhye added.