Alexion has announced positive results from the pivotal phase 3 ALPHA trial showing the efficacy of danicopan as an add-on to standard of care C5 inhibitor therapy in patients with paroxysmal nocturnal hemoglobinuria (PNH) who experience clinically significant extravascular hemolysis (EVH).

“While EVH is not life-threatening, its manifestations can be burdensome for patients. The ALPHA trial demonstrated that adding danicopan to standard of care with eculizumab or ravulizumab significantly improved fatigue and anemia and reduced transfusion dependence, while still allowing for sustained control of IVH [intravascular hemolysis] with terminal complement inhibition addressing the thrombotic risks associated with PNH,” said Professor Jong Wook Lee, MD, PhD, department of hematology at Seoul St. Mary’s Hospital of The Catholic University of Korea, and investigator in the ALPHA trial.

“These results suggest danicopan has the potential to be an important option for the small subset of patients with PNH who experience clinically significant EVH while being treated with eculizumab or ravulizumab.”

According to the data recently presented at the European Hematology Association (EHA) Annual Meeting in Frankfurt, Germany, danicopan as add-on to ravulizumab-cwvz (Ultomiris®) or eculizumab (Soliris®) was superior to the comparator arm based on change in hemoglobin from baseline to week 12 (primary efficacy endpoint).

Read more about PNH experimental therapies

Significant improvements in hemoglobin were observed with danicopan by week 2 and were sustained through week 12.

Moreover, all key secondary endpoints were met. The proportion of patients showing improvement in hemoglobin greater than or equal to 2 g/dL at week 12, in the absence of transfusion, was superior with danicopan (59.5%) versus placebo (0%).

Further, significantly more patients treated with danicopan avoided transfusion through week 12 versus placebo.

“As a leader in PNH for decades, Alexion has transformed the treatment landscape by developing the first approved medicine for this rare disease and establishing C5 complement inhibition as standard of care. These promising results presented at the EHA Annual Meeting underscore the potential for targeted factor D inhibition with danicopan as an add-on to Ultomiris or Soliris to address clinically significant EVH while allowing patients to maintain disease control with established C5 complement inhibitors,” said Gianluca Pirozzi, senior vice president and head of development, regulatory, and safety at Alexion.

The results have also revealed improvements in fatigue and reticulocyte count, while change from baseline in lactate dehydrogenase suggest effective control of IVH was maintained with C5 inhibition in the treatment and placebo arms.


Danicopan as add-on to ULTOMIRIS® or SOLIRIS® improved hemoglobin levels and maintained disease control in patients with PNH experiencing signs or symptoms of clinically significant extravascular hemolysis. News release. Alexion; June 9, 2023.