Voydeya Approved as Add-On Therapy for Extravascular Hemolysis in PNH

The Food and Drug Administration (FDA) has approved Voydeya^™ (danicopan) as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH).

Voydeya binds reversibly to complement factor D and selectively inhibits the alternative complement pathway. In patients with PNH, Voydeya controls preferentially C3 fragment-mediated EVH, while co-administered ravulizumab or eculizumab (both C5 inhibitors) is expected to maintain control over the membrane attack complex-mediated intravascular hemolysis.

The approval was based on data from the double-blind, placebo-controlled phase 3 ALPHA trial (ClinicalTrials.gov Identifier: NCT04469465), which evaluated the efficacy and safety of danicopan in 63 adults with PNH and clinically significant EVH defined by anemia (hemoglobin [Hgb] ≤9.5g/dL) with absolute reticulocyte count greater than or equal to 120 × 10⁹/L with or without transfusion support. These patients had been receiving a stable dose of ravulizumab or eculizumab for at least the previous 6 months.

Study participants were randomly assigned 2:1 to receive danicopan 150mg orally 3 times a day (escalated to 200mg 3 times a day depending on clinical response) or placebo for 12 weeks, in addition to ravulizumab or eculizumab. After 12 weeks, all patients received danicopan up to week 24 with background ravulizumab or eculizumab. 

Results showed treatment with danicopan met the primary endpoint demonstrating a statistically significant mean increase in Hgb from baseline to week 12 compared with placebo (2.9g/dL vs 0.5g/dL, respectively; treatment difference, 2.4g/dL [95% CI, 1.7-3.2]; P =.0007). 

Moreover, patients who received danicopan met the following key secondary endpoints at week 12 compared with placebo, respectively:

• Proportion of patients with Hgb increase of ≥2g/dL in the absence of transfusion: 59.5% vs 0% (treatment difference, 46.9% [95% CI, 29.2-64.7]; P <.0001);
• Proportion of patients with transfusion avoidance: 83.3% vs 38.1% (treatment difference, 41.7% [95% CI, 22.7-60.8]; P =.0004);
• Mean change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score: 8.0 vs 1.9 (treatment difference, 6.1 [95% CI, 2.3-9.9]; P =.002); and

Mean change in absolute reticulocyte count (10⁹/L): -84 vs 4 (treatment difference, -87 [95% CI, -118, -57]; P <.0001).

The most frequent adverse reaction reported (incidence ≥10%) was headache. The prescribing information for Voydeya also includes a Boxed Warning regarding an increased risk for serious and life-threatening infections caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B.

Because of this risk, Voydeya is available only through a restricted program called Voydeya REMS. Vaccination against encapsulated bacteria or antibacterial drug prophylaxis (in a patient who is not up to date with vaccines) is recommended. The treatment is contraindicated in individuals with unresolved serious infections.

Commenting on the approval, Marc Dunoyer, Chief Executive Officer, Alexion, said: “The approval of first-in-class, factor D inhibitor Voydeya marks an important advancement in the treatment of PNH and builds on our leadership and commitment to bring forward innovation in complement science. As the ALPHA trial suggests, dual complement pathway inhibition at factor D and C5 may be an optimal treatment approach for this subset of patients with EVH, enabling them to continue with proven standard of care therapy.”

Voydeya is supplied as a tablet in 50mg and 100mg dosage strengths.