Danicopan — Drug Monograph

Brand names: Voydeya

Drug class: Other

Mechanism of Action

Danicopan is an oral, small-molecule inhibitor of complement Factor D, a rate-limiting serine protease of the alternative pathway. By inhibiting Factor D, it blocks formation and amplification of the alternative pathway C3 convertase, reducing C3 fragment (C3b) deposition on PNH red cells. Added on to a C5 inhibitor, it specifically controls the extravascular hemolysis mediated by C3 opsonization while the C5 inhibitor continues to block terminal intravascular hemolysis. It is not used as monotherapy in PNH.

FDA Indications

• Add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH) (approved 2024)

Common Side Effects

• Headache
• Nausea
• Arthralgia
• Diarrhea
• Cough
• Pyrexia
• Nasopharyngitis
• Abdominal pain
• Peripheral edema

Clinical Pearl

In the Phase 3 ALPHA trial, adding danicopan to eculizumab or ravulizumab significantly raised hemoglobin (mean increase around 3 g/dL at 12 weeks) and reduced transfusion dependence in patients with clinically significant extravascular hemolysis, a limitation of C5 inhibitors alone. It is specifically a Factor D add-on and must never be used without an active C5 inhibitor, since stopping the C5 inhibitor exposes patients to catastrophic intravascular hemolysis.

Related Therapies & Mechanisms

• Iptacopan (Fabhalta) — Other · PNH
• Pegcetacoplan (Empaveli) — Other · PNH
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other