Iptacopan — Drug Monograph
Brand names: Fabhalta
Drug class: Other
Mechanism of Action
Iptacopan is an oral, first-in-class small-molecule inhibitor that binds Factor B and inhibits the alternative pathway C3 convertase (C3bBb). By acting proximally and selectively on the alternative complement pathway, it controls both C3b deposition and downstream terminal pathway activation. In PNH this simultaneously prevents intravascular hemolysis (terminal complement) and the extravascular hemolysis driven by C3 opsonization, while sparing the classical and lectin pathways. Its target position upstream of C3 allows effective control as oral monotherapy.
FDA Indications
- Paroxysmal nocturnal hemoglobinuria (PNH) in adults (approved December 2023)
- Reduction of proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression (2024)
- Complement 3 glomerulopathy (C3G) to reduce proteinuria in adults (2025)
Common Side Effects
- Headache
- Nasopharyngitis
- Diarrhea
- Abdominal pain
- Nausea
- Upper respiratory tract infection
- Bacterial infection
- Arthralgia
- Dizziness
Clinical Pearl
In APPLY-PNH (patients with residual anemia on a C5 inhibitor) and APPOINT-PNH (complement-inhibitor-naive patients), oral iptacopan monotherapy produced clinically meaningful hemoglobin increases of at least 2 g/dL and transfusion avoidance in the majority of patients without any C5 inhibitor. Its oral twice-daily dosing and control of both intravascular and extravascular hemolysis make it the first effective oral monotherapy for PNH.
Related Therapies & Mechanisms
- Danicopan (Voydeya) — Other · PNH
- Pegcetacoplan (Empaveli) — Other · PNH
- Adagrasib (Krazati) — Other
- Arsenic Trioxide (Trisenox) — Other