Alexion announced positive results from the 24-week and long-term extension (LTE) period of the pivotal ALPHA Phase III trial showed danicopan as add-on to standard of care C5 inhibitor therapy ULTOMIRIS (ravulizumab-cwvz) or SOLIRIS (eculizumab) continued to demonstrate clinical benefit for patients with paroxysmal nocturnal hemoglobinuria (PNH) who experience clinically significant extravascular hemolysis (EVH). Results from the trial were presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California. Danicopan is an investigational, first-in-class, oral, Factor D inhibitor.

Data showed that improvements in mean hemoglobin levels and absolute reticulocyte count (ARC) levels, which were demonstrated at 12 weeks, were maintained through 48 weeks. The pivotal ALPHA Phase III trial is designed as a superiority study to evaluate the efficacy and safety of danicopan as an add-on to C5 inhibitor therapy ULTOMIRIS or SOLIRISin patients with PNH who experience clinically significant EVH. A total of 86 patients were randomized.

The prespecified interim analysis (primary analysis) occurred after 63 participants either completed or discontinued from the primary treatment period of 12 weeks. Following the 12-week randomized control period, patients were eligible to enroll in an open-label treatment period for an additional 12 weeks. During the open-label period, participants receiving placebo plus ULTOMIRIS or SOLIRIS switched to danicopan plus ULTOMIRIS or SOLIRIS (placebo-danicopan), and participants receiving add-on therapy with danicopan continued treatment with danicopan add-on therapy (danicopan-danicopan).

The open-label treatment period was followed by the option to join a two-year LTE period during which all participants received danicopan add-on therapy. At the time of data cut-off on September 20, 2022, 60 of the 63 patients who were included in the primary analysis had reached 24 weeks and entered the LTE.1 Data showed that the significant improvements in hemoglobin levels observed at 12 weeks [LSM (SEM) change 2.94 (0.21) g/dL] continued at 24 weeks [LSM (SEM) change 3.17 (0.30) g/dL] among patients treated with danicopan plus ULTOMIRISor SOLIRIS and were sustained through 48 weeks. Secondary endpoints measured at 24 weeks include change from baseline in hemoglobin, ARC, and lactate dehydrogenase (LDH) levels; the percentage of patients with hemoglobin increase of =2 g/dL in the absence of transfusion; and the percentage of patients with transfusion avoidance.

All key secondary endpoints met superiority in favor of danicopan plus ULTOMIRISor SOLIRIS compared to placebo plus ULTOMIRIS or SOLIRIS at 12 weeks, and data showed benefits were maintained at 24 weeks in the danicopan-danicopan arm. Further, all key secondary endpoints showed meaningful improvement at 24 weeks in patients who switched from placebo to add-on treatment with danicopan at 12 weeks,including ARC levels and percentage of patients with transfusion avoidance, two indicators of potential EVH.1 Additionally, mean (SD) LDH levels were maintained from baseline through 48 weeks in both treatment arms, demonstrating effective control of terminal complement activity and IVH with ULTOMIRISor SOLIRIS.