Review
Copyright ©The Author(s) 2017.
World J Cardiol. Feb 26, 2017; 9(2): 76-91
Published online Feb 26, 2017. doi: 10.4330/wjc.v9.i2.76
Table 1 Summary of phase III ODYSSEY trials with Alirocumab
Name of trialRef. Allocation and blindingNo. of patientsInclusion criteriaStudy arms (with dosing)Primary end pointResults
LONG TERM (NCT01507831)Seidah et al[7]; Randomized double blinded trial2341Either 1 or 2 below and who aren’t adequately controlled with their LLT: (1) Patients with heFH with or without CHD or CHD risk equivalents OR (2) Patients with HCL with CHD or CHD risk equivalentsAlirocumab (SC) (n = 1553) vs Placebo (SC) (n = 788) both with background LLTPercentage change in calculated LDL cholesterol level from baseline to week 24-61.0% change with Alirocumab vs +0.8% change with placebo (CI: -64.3 to -59.4; P < 0.001)
FH I (NCT01623115)Kastelein et al[66]; Randomized double blinded486Patients with heterozygous familial hypercholesterolemia who are not adequately controlled with their lipid-modifying therapyAlirocumab (SC) vs Placebo (SC) both with background LLTPercent change in calculated LDL-C at week 24-48.8% for Alirocumab compared with 9.1% for placebo (P < 0.0001)
FH II (NCT01709500)Kastelein et al[66]; Randomized double blinded249Patients with heFH who are not adequately controlled with their LLTAlirocumab (SC) vs Placebo (SC) both with background LLTPercent change in LDL-C to week 24-48.7% for Alirocumab compared with 2.8% for placebo (P < 0.0001)
HIGH FH (NCT01617655)Kastelein et al[67]; Randomized double blinded107Patients with heterozygous familial hypercholesterolemia who are not adequately controlled with their lipid-modifying therapy with LDL > 160Alirocumab (SC) (n = 72) vs Placebo (SC) (n = 35) both with background LLTPercent change in calculated LDL-C at week 24Percent decrease from baseline was 45.7% vs 6.6%, difference 39.1, P < 0.0001 Absolute difference in values of LDL-C at 24 wk 107 mg/dL vs 182 mg/dL
COMBO I (NCT01644175)Colhoun et al[60]; Randomized double blinded316Patients with hypercholesterolemia and estbl CHD or CHD risk equivalents; not controlled with a maximally tolerated LLT, both at stable dose for at least 4 to 6 wk prior to screeningAlirocumab (SC) (n = 205) vs Placebo (SC) (n = 106)Percent change in calculated LDL-C at week 24-48.2% with Alirocumab (CI: -52.0% to -44.4%) and -2.3% with placebo (CI: -7.6% to 3.1%) for Alirocumab and placebo, respectively, an estimated mean difference of -45.9% (CI: -52.5% to -39.3%) (P < 0.0001)
COMBO II (NCT01644188)Moriarty et al[65]; Randomized double blind720Patients with hypercholesterolemia and established CHD or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin at stable dose for at least 4 wk prior to the screening visitAlirocumab (SC) + placebo (for ezetimibe) orally + background statin therapy (n = 467) vs Placebo (SC) + ezetimibe orally + Background statin therapy (n = 240)Percent change in calculated LDL-C at week 24Reductions in LDL-C from baseline were 50.6% ± 1.4% for Alirocumab vs 20.7% ± 1.9% for ezetimibe (difference 29.8% ± 2.3%; P < 0.0001)
OPTIONS I (NCT01730053)Robinson et al[63]; Randomized double-blinded355Patients with prior CV disease + LDL-C ≥ 70 mg/dL, or CV risk factors + LDL-C ≥ 100 mg/dLAlirocumab with atorvastatin 20 mg vs Ezetimibe with atorvastatin 20 mg vs Atorvastatin 40 mgPercent change in calculated LDL-C to week 24Percent reduction from baseline 44.1% (Alirocumab) vs 20.5% (ezetimibe) vs 5.0% (atorvastatin 40); P < 0.0001
Alirocumab with atorvastatin 40 mg vs ezetimibe with atorvastatin 40 mg vs atorvastatin 80 mg vs rosuvastatin 20 mgPercent reduction from baseline 54% (Alirocumab) vs 22.6% (Ezetimibe) vs 4.8% (Atorvastatin 80) vs 21.4% (rosuvastatin 40); P < 0.0001
OPTIONS IIRobinson et al[63]; Randomized double-blinded305Patients with prior CV disease + LDL-C ≥ 70 mg/dL, or CV risk factors + LDL-C ≥ 100 mg/dLAlirocumab with rosuvastatin 10 mg vs ezetimibe with rosuvastatin 10 vs rosuvastatin 20Percent change in calculated LDL-C to wk 24Percent reduction from baseline 50.6% (Alirocumab) vs 14.4% (ezetimibe) vs 16.3% (rosuvastatin 20); P < 0.0001
Alirocumab with rosuvastatin 20 mg vs ezetimibe with rosuvastatin 20 vs Rosuvastatin 40Percent reduction from baseline 36.3% (Alirocumab) vs 11.0% (Ezetimibe) vs 20.3% (rosuvastatin 40); P < 0.0001
ALTERNATIVE (NCT01709513)Moriarty et al[65]; Randomized double-blinded314Primary heFH with moderate, high or very high CV risk and history of statin intoleranceAlirocumab + oral placebo vs ezetimibe (10 mg/d) + sc placebo vs atorvastatin (20 mg/d) + sc placeboPercent change in calculated LDL-C to week 24 in intention to treat groupPercent reduction from baseline 45% (Alirocumab) vs 14.6% (Ezetimibe) with a mean difference of -30.4%; P < 0.0001
CHOICE I (NCT01926782)Stroes et al[78]; Randomized, double-blinded803Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD riskAlirocumab at q4 week regimen vs PlaceboPercent change in LDL from baseline to week 24 for Alirocumab q4w vs placebo in patients with hypercholesterolemia at moderate, high, or very high CVD risk with concomitant statin therapy (n = 547) Percent change in LDL from baseline to week 24 for Alirocumab q4w vs placebo in patients with hypercholesterolemia not on concomitant statin therapy (n = 256)LDL was reduced by 58.7% with Alirocumab in patients on maximally tolerated statins (P < 0.001)
CHOICE II (NCT02023879)Stroes et al[78]; Randomized, double-blinded231Patients with primary hypercholesterolemia (heFH or non-FH) not adequately controlled with their non statin lipid modifying therapy or diet and statin intoleranceAlirocumab (SC) vs placebo (SC)The percent change in LDL-C from baseline to week 24Alirocumab reduced LDL-C by 56.4% (P < 0.0001) vs placebo
LONG TERM (NCT01507831)Robinson et al[62]; Randomized, double-blinded2341Either A or B below and who are not adequately controlled with their LLT: (1) Patients with heFH with or without established CHD or CHD risk equivalents OR (2) Patients with hypercholesterolemia together with established CHD or CHD risk equivalentsAlirocumab (SC) 150 mg every 2 wk vs placebo (SC) every 2 wkPercentage change in calculated LDL cholesterol level from baseline to week 24, analyzed with the use of an intention-to-treat approach150 mg Alirocumab every 2 wk had a 62% reduction in LDL as opposed to a 1% increase in LDL with placebo at 24 wk