RODRIGO SOUZA

Biocatalysis and Organic Synthesis Group, Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Iptacopan (Fabhalta) was approved in December 2023 by the US Food and Drug Administration (FDA) as a first-in-class complement factor B inhibitor indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening blood disorder characterized by complement-driven hemolysis, thrombosis and impaired bone marrow function, resulting in anemia, fatigue, and other debilitating symptoms. Current treatments for patients with PNH include the complement C5 inhibitors eculizumab and ravulizumab which prevent intravascular hemolysis, and the complement C3 inhibitor pegcetacoplan which prevents both intravascular and extravascular hemolysis. Now, patients with PNH have oral alternative to the drugs Soliris and Ultomiris, which are widely used to treat the serious blood disorder.

Novartis has forecast sales of iptacopan reaching beyond $2 billion a year and is developing it for an array of other complement-mediated kidney diseases including C3 glomerulopathy, IgA nephropathy and atypical hemolytic uremic syndrome.

Synthesis of iptacopan hydrochloride starts with the metalation o ...