Factor D Inhibitor Wins Approval for PNH With Extravascular Hemolysis

The FDA approved the oral factor D inhibitor danicopan (Voydeya) as an add-on therapy to treat extravascular hemolysis in adults with paroxysmal nocturnal hemoglobinuria (PNH), AstraZeneca announced.

The approval specifies use of the first-in-class agent with ravulizumab (Ultomiris) or eculizumab (Soliris), standard-of-care treatment for PNH. Anywhere from 10-20% of patients with PNH develop significant extravascular hemolysis during treatment with a C5 inhibitor.

“The approval of Voydeya offers this small subset of PNH patients an add-on therapy designed to address [extravascular hemolysis] while maintaining disease control with Ultomiris or Soliris,” said Bart Scott, MD, of the University of Washington and Fred Hutchinson Cancer Center in Seattle, in a statement from the drugmaker.

Principal support for the approval came from the randomized phase III ALPHA trial, which evaluated standard treatment with or without danicopan in 73 patients with PNH and significant extravascular hemolysis (hemoglobin ≤9.5 g/dL, absolute reticulocyte count ≥120 × 10⁹/L). The trial met the primary endpoint of change in hemoglobin from baseline to 12 weeks. At the planned interim analysis, patients randomized to danicopan had an improvement in mean hemoglobin level of 2.94 g/dL as compared with 0.50 g/dL in the placebo arm (P<0.0001). The trial also met all key secondary endpoints, including transfusion avoidance and change in fatigue score.

Danicopan was generally well tolerated, and no new or unexpected safety concerns arose during the study. The most common treatment-emergent adverse events were headache, nausea, arthralgia, and diarrhea.

According to AstraZeneca, the drug “works by selectively inhibiting factor D, a complement system protein that plays a key role in the amplification of the complement system response. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells.”

Danicopan was previously approved in Japan and has received a recommendation for approval by the European Union.

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