Photo from EHA
Session at the 23rd Congress of the European Hematology Association (EHA)
STOCKHOLM—Results of a phase 3 study suggest the long-acting C5 complement inhibitor ravulizumab produces similar results as eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH).
Treatment with ravulizumab every 8 weeks proved noninferior to treatment with eculizumab every 2 weeks for the co-primary endpoints of transfusion avoidance and hemolysis as measured by lactate dehydrogenase (LDH) normalization.
Ravulizumab also proved noninferior with regard to secondary efficacy endpoints and had a safety profile similar to that of eculizumab.
These results suggest ravulizumab could be a more convenient alternative for PNH patients, according to Jong Wook Lee, MD, of Seoul St. Mary’s Hospital in Seoul, South Korea.
Dr Lee presented these results as a late-breaking abstract (LB2603) at the 23rd Congress of the European Hematology Association (EHA).
The study was sponsored by Alexion Pharmaceuticals.
The trial enrolled adults with PNH naive to complement inhibitor therapy. They were randomized to receive ravulizumab (n=125) or eculizumab (n=121) for 183 days.
More than half of patients were male—52% in the ravulizumab arm and 57% in the eculizumab arm. Most patients were Asian (57.6% in the ravulizumab arm and 47.1% in the eculizumab arm) or white (34.4% and 42.1%, respectively).
Patients’ mean age at first infusion was 44.8 in the ravulizumab arm and 46.2 in the eculizumab arm. The mean number of years from PNH diagnosis to consent was 6.7 and 6.4, respectively.
The mean LDH at baseline was 1634 U/L in the ravulizumab arm and 1578 U/L in the eculizumab arm. The mean FACIT-Fatigue score was 36.7 and 36.9, respectively.
All 125 ravulizumab patients completed 26 weeks of treatment, as did 119 of the eculizumab patients. One hundred twenty-four ravulizumab patients entered the extension phase, as did 119 eculizumab patients.
Efficacy
The study’s primary efficacy endpoints were transfusion avoidance and LDH normalization from day 29 to 183. Dr Lee said ravulizumab proved noninferior to eculizumab for both endpoints, and point estimates favored ravulizumab.
The proportion of patients who remained transfusion-free was 73.6% in the ravulizumab arm and 66.1% in the eculizumab arm (difference, 6.8; 95% CI, -4.66, 18.14).
The proportion of patients who achieved LDH normalization was 53.6% and 49.4%, respectively (difference, 1.19; 95% CI, 0.8, 1.77).
Secondary efficacy endpoints included the percentage change in LDH from baseline, change in FACIT-Fatigue score from baseline, and the proportions of patients with breakthrough hemolysis and stabilized hemoglobin.
Again, ravulizumab was noninferior to eculizumab for all endpoints, with point estimates favoring ravulizumab.
The LDH percentage change was -76.84% in the ravulizumab arm and -76.02% in the eculizumab arm (difference, 0.83; 95% CI, -3.56, 5.21).
The change (improvement) in FACIT-Fatigue score was 7.07 and 6.40, respectively (difference, 0.67; 95% CI, -1.21, 2.55).
The percentage of patients with hemoglobin stabilization was 68.0% in the ravulizumab arm and 64.5% in the eculizumab arm (difference, 2.9; 95% CI, -8.80, 14.64).
The percentage of patients with breakthrough hemolysis was 4.0% and 10.7%, respectively (difference, 6.7; 95% CI, -0.18, 14.21).
Dr Lee noted that the proportion of patients with breakthrough hemolysis was more than 2.5-fold higher in the eculizumab arm than the ravulizumab arm—13 patients with 15 events and 5 patients with 5 events, respectively.
He said this was likely due to the immediate, complete, and sustained inhibition of C5 (mean free C5 <0.5 μg/mL) achieved by ravulizumab. Complete inhibition was observed after the first ravulizumab infusion and was sustained throughout the 26-week treatment period.
Safety
Dr Lee said ravulizumab had a similar safety profile to eculizumab, and both drugs were well tolerated.
Most patients experienced a treatment-emergent adverse event (TEAE)—88% in the ravulizumab arm and 86.8% in the eculizumab arm.
The most common TEAEs (in the ravulizumab and eculizumab arms, respectively) were headache (36.0% and 33.1%), nasopharyngitis (8.8% and 14.9%), upper respiratory tract infection (10.4% and 5.8%), and pyrexia (4.8% and 10.7%).
Serious AEs occurred in 8.8% of patients in the ravulizumab arm and 7.4% of those in the eculizumab arm.
Major adverse vascular events occurred in 2 patients in the ravulizumab arm and 1 in the eculizumab arm. There were no meningococcal infections in either arm.
One patient in the eculizumab arm was discontinued from the study and died of lung cancer (which was unrelated to treatment).