Table 1.
Demographics, Baseline Characteristics, and Treatment-Emergent Adverse Events
| Demographics and Baseline Characteristics | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1a | 25 mg SC (n = 2) | 75 mg SC (n = 6) | 75 mg IV (n = 6) | 150 mg SC (n = 6) | 300 mg SC (n = 6) | 450 mg SC (n = 6) | 450 mg IV (n = 6) | 600 mg SC (n = 6) | Tafolecimab (n = 44) | Placebo (n = 14) |
| Age, y | 28-30 | 29.3 ± 6.3 | 33.3 ± 3.7 | 28.7 ± 6.5 | 27.7 ± 5.8 | 34.3 ± 4.7 | 29.8 ± 6.8 | 29.0 ± 6.1 | – | 29.8 ± 6.0 |
| Male | 2 (100) | 4 (67) | 6 (100) | 4 (67) | 4 (67) | 4 (67) | 5 (83) | 3 (50) | – | 12 (86) |
| BMI, kg/m2 | 20.7-23.4 | 22.8 ± 1.4 | 23.1 ± 1.9 | 25.2 ± 2.7 | 23.8 ± 1.8 | 23.8 ± 2.0 | 22.1 ± 2.6 | 23.1 ± 2.4 | – | 23.8 ± 2.7 |
| LDL-C, mmol/L | 2.0-3.0 | 2.6 ± 0.6 | 3.2 ± 0.7 | 3.1 ± 0.8 | 2.7 ± 0.5 | 2.8 ± 0.7 | 2.5 ± 0.3 | 3.0 ± 0.7 | – | 3.0 ± 0.6 |
| PCSK9, ng/mL | 422.7-588.6 | 445.3 ± 134.3 | 500.7 ± 146.5 | 497.1 ± 70.0 | 365.7 ± 73.9 | 429.4 ± 107.1 | 432.7 ± 55.2 | 450.4 ± 126.1 | – | 437.9 ± 82.2 |
| Phase 1b | 75 mg Q2W (n = 8) | 140 mg Q2W (n = 8) | 300 mg Q4W (n = 8) | 420 mg Q4W (n = 8) | 450 mg Q6W (n = 8) | 600 mg Q6W (n = 8) | Tafolecimab (n = 48) | Placebo (n = 12) | ||
| Age, y | 58.8 ± 6.2 | 54.5 ± 12.4 | 53.6 ± 6.4 | 52.8 ± 13.6 | 47.1 ± 10.4 | 55.9 ± 9.8 | – | 44.3 ± 17.8 | ||
| Male | 3 (38) | 1 (13) | 0 | 4 (50) | 4 (50) | 4 (50) | – | 5 (42) | ||
| BMI, kg/m2 | 26.2 ± 1.8 | 24.4 ± 2.2 | 26.0 ± 2.2 | 23.0 ± 3.3 | 24.65 ± 2.1 | 24.0 ± 1.9 | – | 24.9 ± 3.3 | ||
| LDL-C, mmol/L | 4.4 ± 0.9 | 3.8 ± 0.8 | 3.9 ± 0.4 | 3.9 ± 0.5 | 3.6 ± 0.6 | 3.7 ± 0.6 | – | 3.8 ± 0.6 | ||
| PCSK9, ng/mL | 546.5 ± 98.0 | 577.3 ± 130.0 | 582.6 ± 156.8 | 532.6 ± 96.4 | 596.2 ± 131.9 | 507.7 ± 171.0 | – | 594.4 ± 134.0 | ||
| Treatment-Emergent Adverse Events | ||||||||||
| Phase 1a | 25 mg SC (n = 2) | 75 mg SC (n = 6) | 75 mg IV (n = 6) | 150 mg SC (n = 6) | 300 mg SC (n = 6) | 450 mg SC (n = 6) | 450 mg IV (n = 6) | 600 mg SC (n = 6) | Tafolecimab (n = 44) | Placebo (n = 14) |
| Any event | 1 (50) | 2 (33) | 4 (67) | 4 (67) | 3 (50) | 1 (17) | 4 (67) | 4 (67) | 23 (52) | 8 (57) |
| Adverse events that occurred in ≥5% of participants in phase 1a cohorts (n = 58) | ||||||||||
| Upper respiratory tract infection | 0 | 0 | 2 (33) | 2 (33) | 0 | 0 | 2 (33) | 3 (50) | 9 (21) | 2 (14) |
| Blood creatine phosphokinase increase | 0 | 1 (17) | 2 (33) | 1 (17) | 1 (17) | 0 | 0 | 1 (17) | 6 (14) | 0 |
| Blood uric acid increase | 0 | 0 | 1 (17) | 0 | 0 | 1 (17) | 0 | 0 | 2 (5) | 2 (14) |
| Phase 1b | 75 mg Q2W (n = 8) | 140 mg Q2W (n = 8) | 300 mg Q4W (n = 8) | 420 mg Q4W (n = 8) | 450 mg Q6W (n = 8) | 600 mg Q6W (n = 8) | Tafolecimab (n = 48) | Placebo (n = 12) | ||
| Any event | 7 (88) | 7 (88) | 7 (88) | 5 (63) | 3 (38) | 5 (63) | 34 (71) | 9 (75) | ||
| Adverse events that occurred in ≥5% of patients in phase 1b cohorts (n = 60) | ||||||||||
| Upper respiratory tract infection | 2 (25) | 0 | 3 (38) | 3 (38) | 0 | 1 (13) | 9 (19) | 1 (8) | ||
| Blood pressure increase | 0 | 0 | 2 (25) | 0 | 1 (13) | 1 (13) | 4 (8) | 1 (8) | ||
| Asthenia | 0 | 0 | 4 (50) | 0 | 0 | 0 | 4 (8) | 0 | ||
| White blood cell count increase | 0 | 1 (13) | 0 | 0 | 0 | 1 (13) | 2 (4) | 2 (17) | ||
| Neutrophil count decrease | 0 | 1 (13) | 0 | 0 | 1 (13) | 0 | 2 (4) | 1 (8) | ||
| White blood cells urine positive | 0 | 1 (13) | 0 | 0 | 2 (25) | 0 | 3 (6) | 0 | ||
| Electrocardiogram QT prolonged | 0 | 0 | 2 (25) | 0 | 0 | 1 (13) | 3 (6) | 0 | ||
| White blood cell count decrease | 0 | 1 (13) | 0 | 0 | 1 (13) | 0 | 2 (4) | 1 (8) | ||
| Arthralgia | 2 (25) | 0 | 0 | 1 (13) | 0 | 0 | 3 (6) | 0 | ||
Values are range, mean ± SD, or n (%).
BMI = body mass index; IV = intravenously; LDL-C = low-density lipoprotein cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9; Q2W, Q4W, Q6W = every 2, 4, 6 weeks; SC = subcutaneously.