Iptacopan

Iptacopan, sold under the brand name Fabhalta, is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria. It is a complement factor B inhibitor that was developed by Novartis. It is taken by mouth.

Iptacopan was approved by the US Food and Drug Administration (FDA) for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023. The FDA considers it to be a first-in-class medication.

Medical uses
Iptacopan is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria.

Mechanism of action
Iptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway.

In PNH, intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC), while extravascular hemolysis (EVH) is facilitated by C3b opsonization. Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated EVH and terminal complement mediated IVH.

Side effects
The FDA label for iptacopan contains a black box warning for the risk of serious and life-threatening infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B.

Legal status
In March 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Fabhalta, intended for the treatment of paroxysmal nocturnal haemoglobinuria (PNH). The applicant for this medicinal product is Novartis Europharm Limited. Iptacopan was approved for medical use in the European Union in May 2024.

Research
In a clinical study with twelve participants, iptacopan as a single drug led to the normalization of hemolytic markers in most patients, and no serious adverse events occurred during the 12-week study.

Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related macular degeneration and some types of glomerulopathies.