tion described in the table below.
Table 7: Efficacy Results in the Complement-Inhibitor Naïve Study
Statistic for Treatment
ULTOMIRIS Eculizumab Comparison Effect
(N=125) (N=121) (95% CI)
Transfusion 73.6% 66.1% Difference in 6.8
avoidance rate rate (-4.66, 18.14)
LDH normalization 53.6% 49.4% Odds ratio 1.19
(0.80, 1.77)
LDH percent change -76.84% -76.02% Difference in -0.83
% change from (-5.21, 3.56)
baseline
Breakthrough 4.0% 10.7% Difference in -6.7
hemolysis rate (-14.21, 0.18)
Hemoglobin 68.0% 64.5% Difference in 2.9
stabilization rate (-8.80, 14.64)
Note: LDH = lactate dehydrogenase; CI = confidence interval
For the transfusion avoidance endpoint, treatment differences (95% CIs) are based on estimated differencesin percent with 95% CI. For the lactate dehydrogenase normalization endpoint, the adjusted preva lencewithin each treatment is displayed.
There was no observable difference in fatigue between ULTOMIRIS and eculizumabafter 26 weeks of treatment compared to baseline as measured by the FACIT-fatigueinstrument. Patient-reported fatigue may be an under-or over-estimation, becausepatients were not blinded to treatment assignment.
14.2 Study in Eculizumab-Experienced Patients with PNH
The study in eculizumab-experienced patients [ALXN1210-PNH-302; NCT03056040]was a 26-week, multicenter, open-label, randomized, active-controlled, non-inferiority
Phase 3 study conducted in 195 patients with PNH who were clinically stable afterhaving been treated with eculizumab for at least the past 6 months.
Patients who demonstrated clinically stable disease after being treated with eculizumabfor at least the prior 6 months were randomized 1:1 to either continue eculizumab or toswitch to ULTOMIRIS. The mean total PNH granulocyte clone size was 83%, the meanotal PNH monocyte clone size was 86%, and the mean total PNH RBC clone size was60%. Ninety five percent of patients had a documented PNH-associated conditiondiagnosed prior to enrollment on the trial: anemia (67%), hematuria or hemoglobinuria(49%), history of aplastic anemia (37%), history of renal failure (9%), myelodysplasticsyndrome (5%), pregnancy complication (7%), and other (14%). Major baselinecharacteristics were balanced between the two treatment groups.
Table 8: Baseline Characteristics in Eculizumab-Experienced Patients with
PNH
Parameter Statistics
ULTOMIRIS
(N = 97)
Eculizumab
(N = 98)
Age (years) at first infusion in study Mean (SD)
Min, max
46.6 (14.41)
18, 79
48.8 (13.97)
23, 77
Race
White
Asian
Black or African American
Other
Not reported
Unknown
Multiple
n (%)
50 (51.5)
23 (23.7)
5 (5.2)
2 (2.1)
13 (13.4)
3 (3.1)
1 (1.0)
61 (62.2)
19 (19.4)
3 (3.1)
1 (1.0)
13 (13.3)
1 (1.0)
0
Sex
Male
n (%)
50 (51.5) 48 (49.0)
Pre-treatment LDH levels (U/L) Median
Min, max
224.0
135.0, 383.5
234.0
100.0, 365.5
Units of pRBC/whole blood
transfused within 12 months prior to
first dose
Median
Min, max
4.0
(1, 32)
2.5
(2, 15)
Antithrombotic agents used within 28
days prior to first dose
n (%) 20 (20.6) 13 (13.3)
Patients with a history of MAVEa n (%) 28 (28.9) 22 (22.4)
Patients with a history of thrombosis n (%) 27 (27.8) 21 (21.4)
Patients with concomitant
anticoagulant treatment
n (%) 22 (22.7) 16 (16.3)
a MAVE = m |
