Hemolysis, LDH normalization, and breakthrough hemolysis
| . | Study 201 . | Study 103 . | ||||
|---|---|---|---|---|---|---|
| Cohort 1: . | Cohort 2: . | Cohort 3: . | Cohort 4: . | Cohort 1: . | Cohort 2: . | |
| 1000 mg q4w, . | 1600 mg q6w, . | 2400 mg q8w, . | 5400 mg q12w, . | 900 mg q4w, . | 1800 mg q4w, . | |
| n = 6 . | n = 6 . | n = 7 . | n = 7 . | n = 6 . | n = 7 . | |
| LDH reduction from baseline, mean (SD),* % | 72.85 (12.082) | 77.82 (6.474) | 84.96 (4.423) | 89.58 (3.037)† | 85.95 (3.190) | 84.74 (3.774) |
| LDH at end point,‡ mean (SD), U/L | 230.00 (44.018) | 266.00 (54.262) | 306.14 (130.664) | 228.33 (52.997)† | 232.00 (82.292) | 227.86 (50.581) |
| LDH normalization achievement, days 29-253,§n (%) | ||||||
| LDH normalized | 5 (83.3) | 3 (50.0) | 4 (57.1) | 5 (71) | 4 (66.7) | 6 (85.7) |
| LDH ≥1.5× ULN | 4 (66.7) | 3 (50.0) | 2 (28.6) | 3 (43) | 2 (33.3) | 1 (14.3) |
| LDH >2× ULN | 2 (33.3) | 1 (16.7) | 2 (28.6) | 1 (14) | 1 (16.7) | 0 |
| No., weighted average proportion of instances of LDH normalization, days 29-253, n (%) | ||||||
| LDH normalized | 38 (54.3) | 22 (31.4) | 37 (44.6) | 43 (52.4) | 36 (54.5) | 48 (62.3) |
| Breakthrough hemolysis, days 29-253,||n (%) | ||||||
| Incidence of breakthrough hemolysis through end point‡ | 2 (33.3) | 1 (16.7) | 2 (28.6) | 1 (14.3) | 1 (16.7) | 0 (0) |
| . | Study 201 . | Study 103 . | ||||
|---|---|---|---|---|---|---|
| Cohort 1: . | Cohort 2: . | Cohort 3: . | Cohort 4: . | Cohort 1: . | Cohort 2: . | |
| 1000 mg q4w, . | 1600 mg q6w, . | 2400 mg q8w, . | 5400 mg q12w, . | 900 mg q4w, . | 1800 mg q4w, . | |
| n = 6 . | n = 6 . | n = 7 . | n = 7 . | n = 6 . | n = 7 . | |
| LDH reduction from baseline, mean (SD),* % | 72.85 (12.082) | 77.82 (6.474) | 84.96 (4.423) | 89.58 (3.037)† | 85.95 (3.190) | 84.74 (3.774) |
| LDH at end point,‡ mean (SD), U/L | 230.00 (44.018) | 266.00 (54.262) | 306.14 (130.664) | 228.33 (52.997)† | 232.00 (82.292) | 227.86 (50.581) |
| LDH normalization achievement, days 29-253,§n (%) | ||||||
| LDH normalized | 5 (83.3) | 3 (50.0) | 4 (57.1) | 5 (71) | 4 (66.7) | 6 (85.7) |
| LDH ≥1.5× ULN | 4 (66.7) | 3 (50.0) | 2 (28.6) | 3 (43) | 2 (33.3) | 1 (14.3) |
| LDH >2× ULN | 2 (33.3) | 1 (16.7) | 2 (28.6) | 1 (14) | 1 (16.7) | 0 |
| No., weighted average proportion of instances of LDH normalization, days 29-253, n (%) | ||||||
| LDH normalized | 38 (54.3) | 22 (31.4) | 37 (44.6) | 43 (52.4) | 36 (54.5) | 48 (62.3) |
| Breakthrough hemolysis, days 29-253,||n (%) | ||||||
| Incidence of breakthrough hemolysis through end point‡ | 2 (33.3) | 1 (16.7) | 2 (28.6) | 1 (14.3) | 1 (16.7) | 0 (0) |
Primary efficacy end point.
n = 6 for this parameter.
LDH parameters at a protocol-specified end point: Study 103, day 169/24 weeks. Study 201: cohorts 1-3, day 253/36 weeks; cohort 4, day 281/40 weeks.
Patients meeting each parameter at least once after day 29 through day 253. Reference range, 53 to 234 U/L.
Defined as at least 1 symptom or sign of intravascular hemolysis (fatigue, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <100 g/L and hemoglobin less than baseline hemoglobin], MAVE [including thrombosis], dysphagia, or erectile dysfunction) within ±7 days of an elevated LDH ≥2× ULN after prior LDH reduction to <1.5× ULN on therapy.