Table 2.
Key Phase 3 Clinical Trials of Volanesorsen
| Study/Study Population | Primary Objective | Study Design | Dose(mg) | Subjects | Parameters | Placebo Baseline mg/dl (mmol/L) | Placebo On-Treatment mg/dl (mmol/l) | Volanesorsen Baseline mg/dl (mmol/) | Volanesorsen On-Treatment mg/dl (mmol/L) |
Change(%) |
|---|---|---|---|---|---|---|---|---|---|---|
| ISIS304801-CS6 (APPROACH)72 Patients with FCS |
Efficacy Safety | Randomized, Double-Blind, Placebo Controlled, | 300 mg Once weekly for 52 weeks | Volanesorsen: 33 Placebo: 33 |
TG CM-TG ApoB48 ApoB100 ApoC3 |
2152±1153 (24.3±13.0) 1785±1149 (20.2±13.0) 9.3±6.0 69.4±19.8 28.9±13.1 |
2367±1315 (26.7±14.9) 1991±1279 (22.5±14.5) 9.9±6.9 70.4±22.7 30.7±16.1 |
2267±1259 (25.6±14.4) 1913±1216 (21.6±13.7) 11.2±7.1 64.7±19.5 31.4±15.3 |
590±497 (6.7±5.6) 436±480 (4.93±5.4) 2.6±2.4 75.9±27.1 4.6±2.8 |
18 vs.-77 29 vs −83 14 vs −76± 4 vs 20 6 vs −84 |
| ISIS 304801-CS7a (APPROACH OLE)76 Patients with FCS |
Safety | Open-Label Study. | 300 mg Once weekly for 52 weeks |
Volanesorsen: 67 50 naïve 14 CS6 continuing 3 CS16 continuing |
Naïve TG CS6 TG CS16 TG |
2317±1993 (26.1±22.5) 2641±1228 (29.8±13.9 2288±1524 (25.9± 17.2 |
979±683 (11.1±7.7) 1248±927 14.1±10.5) 1558±193 17.6±2.2) |
−47 –55 -39 |
||
| ISIS 304801-CS16b (COMPASS)76 Patients with Hypertriglyceridaemia |
Efficacy Safety |
Randomized, Double-Blind, Placebo Controlled, | 300 mg Once weekly for 26 weeksc |
Volanesorsen: 75 (5 FCS) Placebo: 38 (2 FCS) |
TG | 1414±1253 (16.0±14.2) |
1406±1409 (15.9±15.9) |
1183±759 (13.4±8.6) |
294±245 (3.3±2.8) |
−1 vs −71 |
Notes: aThis is an open-label extension (OLE) study in patients from CS6, CS16, or newly included patients. Data at 6 months. bIncluded patients with FCS. cFor CS16, the protocol was amended so that patients that had not already completed ≥5 months of dosing as of 27 May 2016 had dose frequency reduced to 300 mg every 2 weeks or dose reduced to 150 mg per week after 13 weeks of treatment. A total of 39 patients had their dose or frequency of dosing changed as a consequence of this amendment.