gainst meningococcal infection prior to or at the time ofinitiating treatment with ULTOMIRIS or eculizumab, or received prophylactic treatmentwith appropriate antibiotics until 2 weeks after vaccination. Prophylactic treatment withappropriate antibiotics beyond 2 weeks after vaccination was at the discretion of theprovider.
14.1 Study in Complement-Inhibitor Naïve Patients with PNH
The Complement-Inhibitor Naïve Study [ALXN1210-PNH-301; NCT02946463] was a26-week, multicenter, open-label, randomized, active-controlled, non-inferiority Phase 3
study conducted in 246 patients naïve to complement inhibitor treatment prior to studyentry.
Patients with PNH with flow cytometric confirmation of at least 5% PNH cells wererandomized 1:1 to either ULTOMIRIS or eculizumab. The mean total PNH granulocyte
clone size was 85%, the mean total PNH monocyte clone size was 88%, and the meantotal PNH RBC clone size was 39% . Ninety-eight percent of patients had a documented PNH-associated condition diagnosed prior to enrollment on the trial: anemia (85%),
hemoglobinuria (63%), history of aplastic anemia (32%), history of renal failure (12%),
myelodysplastic syndrome (5%), pregnancy (3%), and other (16%). Major baseline
characteristics were balanced between treatment groups.
Table 6: Baseline Characteristics in the Complement-Inhibitor Naïve Study
Parameter Statistics
ULTOMIRIS
(N = 125)
Eculizumab
(N = 121)
Age (years) at first infusion in study Mean (SD)
Min, max
44.8 (15.2)
18, 83
46.2 (16.2)
18, 86
Sex
Male n (%) 65 (52.0) 69 (57.0)
Race
Asian
White
Black or African American
American Indian or Alaska Native
Other
Not reported
n (%)
72 (57.6)
43 (34.4)
2 ( 1.6)
1 ( 0.8)
4 ( 3.2)
3 ( 2.4)
57 (47.1)
51 (42.1)
4 ( 3.3)
1 ( 0.8)
4 ( 3.3)
4 ( 3.3)
Pre-treatment LDH levels (U/L)
Median
Min, max
1513.5
(378.0, 3759.5)
1445.0
(423.5, 3139.5)
Units of pRBC/whole blood
transfused within 12 months prior to
first dose
Median
Min, max
6.0
(1, 44)
6.0
(1, 32)
Antithrombotic agents used within 28
days prior to first dose
n (%) 22 (17.6) 22 (18.2)
Patients with a history of MAVEb n (%) 17 (13.6) 25 (20.7)
Patients with a history of thrombosis n (%) 17 (13.6) 20 (16.5)
Patients with concomitant
anticoagulant treatment
n (%) 23 (18.4) 28 (23.1)
a “Other” as specified on case report form included thrombocytopenia, chronic kidney disease, andpancytopenia, as well as a number of other conditions.
b MAVE = major adverse vascular eventEfficacy was established based upon transfusion avoidance and hemolysis as directlymeasured by normalization of LDH levels. Transfusion avoidance was defined aspatients who did not receive a transfusion and not meet the protocol specified guidelinesfor transfusion from baseline up to Day 183. Supportive efficacy data included thepercent change from baseline in LDH levels, the proportion of patients with breakthroughemolysis defined as at least one new or worsening symptom or sign of intravascularhemolysis in the presence of elevated LDH ≥ 2 × ULN, after prior LDH reduction to
< 1.5 × ULN on therapy and the proportion of patients with stabilized hemoglobin.
Non-inferiority of ULTOMIRIS to eculizumab was demonstrated across endpoints in thecomplement inhibitor naïve treatment popula |
