On April 1, danicopan (Voydeya) was approved by the U.S. Food and Drug Administration (FDA) as add-on therapy to ravulizumab-cwvz or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH). VOYDEYA is a first-in-class, oral, Factor D inhibitor developed as an add-on to standard-of-care ravulizumab-cwvz or eculizumab to address the needs of the approximately 10% to 20% of patients with PNH who experience clinically significant EVH while being treated with a C5 inhibitor.
The approval was based on positive results from the pivotal ALPHA phase III trial (ClinicalTrials.gov identifier NCT04469465). Results from the 12-week primary evaluation period of the trial were published by Lee et al in December 2023 in The Lancet Haematology.
The ALPHA phase III trial evaluated the efficacy and safety of danicopan as an add-on to ravulizumab or eculizumab in patients with PNH who experienced clinically significant EVH. Results showed that danicopan met the primary endpoint of change in hemoglobin from baseline to week 12 and all key secondary endpoints, including transfusion avoidance and change in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) score. Danicopan was generally well tolerated, and no new safety concerns were identified. In the trial, the most common treatment-emergent adverse events were headache, nausea, arthralgia, and diarrhea.
Danicopan has been granted Breakthrough Therapy designation by the FDA and PRIority MEdicines (PRIME) status by the European Medicines Agency. Danicopan has also been granted Orphan Drug designation in the United States, European Union, and Japan for the treatment of PNH. Danicopan has been approved in Japan and recommended for approval in the European Union; regulatory reviews are ongoing in additional countries.
Bart Scott, MD, Professor, Division of Hematology and Oncology at the University of Washington Medical Center, and Professor, Clinical Research Division at Fred Hutchinson Cancer Center, said, “The approval of [danicopan] offers this small subset of PNH patients an add-on therapy designed to address EVH, while maintaining disease control with [ravulizumab or eculizumab]. Terminal complement inhibition with [ravulizumab] can address the life-threatening complications of PNH, building on the efficacy and safety of [eculizumab] established over nearly 20 years.”
