Rare Daily Staff

Novartis reported positive phase 2 data for its experimental therapy iptacopan, an oral treatment for the rare blood disorder paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, life-threatening disorder characterized by the destruction of oxygen-carrying red blood cells through extravascular and intravascular hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue, hemoglobinuria and difficulty breathing.

Iptacopan is an investigational first-in-class, orally administered targeted factor B inhibitor of the alternative complement pathway. It acts upstream of the C5 terminal pathway, preventing intravascular and extravascular hemolysis in PNH. In doing so, the company said iptacopan may have a therapeutic advantage over current standard-of-care by targeting a key part of the biology responsible for PNH.

Iptacopan is currently in development for a number of complement-driven diseases where significant unmet needs exist, including IgAN, C3G, atypical hemolytic uremic syndrome, and membranous nephropathy. Novartis has initiated a phase 3 study of iptacopan as monotherapy in PNH.

All patients completing at least 12 weeks of iptacopan treatment achieved the primary endpoint of at least a 60 percent reduction in their lactate dehydrogenase levels, a biomarker of intravascular hemolysis. Importantly, with the exception of one patient receiving a single red blood cell (RBC) transfusion, all patients remained transfusion-free through 12 weeks of study. Patients also showed improvement in other biomarkers of hemolysis and a marked increase in the proportion of PNH-type RBCs, indicating overall control of both intra- and extravascular hemolysis.

No serious adverse events or thromboembolic events were reported during the 12-week treatment period and the study yielded no unexpected safety results. Two participants discontinued iptacopan treatment before completing 12 weeks of treatment: one due to a non-serious headache, the other by physician decision due to worsening of pre-existing neutropenia.

The company reported the results at the 26th Annual Congress of the European Hematology Association.

“PNH is a rare and life-threatening blood disorder with often debilitating symptoms,” said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis. “New treatment options are needed, and these positive results further strengthen the profile of iptacopan as a promising oral monotherapy.”

Photo: John Tsai, head of global drug development and chief medical officer of Novartis

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