Table 3.
Summary of results from alirocumab studies in patient groups with unmet needs
| Study | Population | Primary/co-primary endpoints | Efficacy | Safety |
|---|---|---|---|---|
| ODYSSEY LONG TERM [88] (alirocumab vs. PL) | Pts with LDL-C >1.8 mmol/l on maximum-tolerated dose of statins with or without other lipid-lowering therapy; N = 2341 | Percent change in calculated LDL-C level from BL to week 24 | Alirocumab reduced LDL-C by 62 % (p < 0.001) vs. PL by week 24 | Alirocumab vs. PL injection-site reactions (6 vs. 4 %), myalgia (5 vs. 3 %), neurocognitive events (1 vs. 0.5 %), and ophthalmologic events (3 vs. 2 %). In a post hoc analysis, the rate of major adverse CV events was lower with alirocumab than with PL (2 vs. 3 %; p = 0.02) |
| ODYSSEY FH I and FH II [89] (alirocumab 75 mg every 2 weeks vs. PL) | Pts with HeFH and inadequate LDL-C control on maximally tolerated lipid-lowering therapy; N = 735 | Percent change in calculated LDL-C from BL to week 24 (both studies) | Alirocumab reduced LDL-C 58 % vs. PL at week 24 in FH I and by 51 % vs. PL in FH II. LDL-C 1.8 mmol/l (was achieved at week 24 by 60 % and 68 % of alirocumab-treated pts in FH I and FH II, respectively | AE-related tx discontinuation in 3 % of alirocumab-treated pts in FH I (vs. 6 % PL) and 4 % (vs. 1 %) in FH II. Injection-site reactions in alirocumab-treated pts 12 % in FH I and 11 % in FH II (vs. 11 % and 7 % with PL) |
| ODYSSEY HIGH FH [90] (alirocumab 150 mg every 2 weeks vs. PL) | Pts with HeFH and inadequate LDL-C control on maximally tolerated lipid-lowering therapy; N = 107 | Percent change in LDL-C from BL to 24 weeks (ITT) | Alirocumab reduced LDL-C by 46 vs. 7 % with PL (p < 0.0001) | TEAEs were generally comparable between groups: 61 % of pts in the alirocumab group vs. 71 % of pts in the PL group |
| ODYSSEY OPTIONS I [91] (atorvastatin plus alirocumab vs. atorvastatin plus ezetimibe; or double atorvastatin; or rosuvastatin) | Pts with very high CVD risk and LDL-C >70 mg/dl or high CVD risk and LDL-C of >100 mg/dl on BL atorvastatin 20 or 40 mg; N = 355 | Percent change in LDL-C from BL to 24 weeks (ITT) | In atorvastatin 20 and 40 mg regimens, respectively: Add-on alirocumab reduced LDL-C levels by 44 % and 54 % (p < 0.001 vs. all comparators) Add-on ezetimibe, 21 % and 23 % Double atorvastatin dose, 5 % in both cases Switching atorvastatin 40 mg to rosuvastatin 40 mg, 21 % |
TEAEs occurred in 65 % of alirocumab pts vs. 64 % ezetimibe and 64 % double atorvastatin/switch to rosuvastatin (data were pooled) |
| ODYSSEY OPTIONS II [92] (rosuvastatin plus alirocumab vs. rosuvastatin plus ezetimibe; or double-dose rosuvastatin) | Pts with very high CVD risk and LDL-C >70 mg/dl or high CVD risk and LDL-C of >100 on BL rosuvastatin 20 or 40 mg; N = 305 | Percent change in LDL-C from BL to 24 weeks (ITT) | In the BL rosuvastatin 10-mg group, add-on alirocumab reduced LDL-C by 51 % vs. ezetimibe (14 %) and double-dose rosuvastatin (16 %) (p < 0.0001 in both cases). In the BL rosuvastatin 20-mg group, add-on alirocumab reduced LDL-C by 36 % vs. ezetimibe (11 %) and double-dose rosuvastatin (16 %) (p = 0.0136 and p = 0.0453, respectively; pre-specified threshold for significance, p < 0.0125) | TEAEs occurred in 56 % of alirocumab pts vs. 54 % ezetimibe and 67 % double-dose rosuvastatin (data were pooled) |
| ODYSSEY ALTERNATIVE [93] (alirocumab vs. ezetimibe) | Statin-intolerant pts with very high BL LDL-C levels; N = 314 | Percent reductions in LDL-C at week 24 | Significantly more pts achieved LDL-C goals with alirocumab than with ezetimibe (42 vs. 4 %, p < 0.0001) | Alirocumab was better tolerated than atorvastatin (HR 1.63, p = 0.042) with a significantly lower rate of skeletal muscle adverse events (p < 0.05) |
| ODYSSEY COMBO I [94] (alirocumab vs. PL) | Pts with high CV risk with sub-optimally controlled hypercholesterolemia on maximum tolerated dose of statins with or without other lipid-lowering therapy; N = 316 | Percent change in LDL-C from BL to 24 weeks (ITT) | Alirocumab reduced LDL-C by 48 vs. 2 % with PL (p < 0.0001) | TEAEs (76 % of pts in both groups) and tx-emergent serious AEs (13 % of pts in both groups) were similar in the alirocumab and PL groups |
| ODYSSEY COMBO II [95] (alirocumab vs. ezetimibe) | Pts with high CV risk with suboptimally-controlled hypercholesterolaemia on maximum tolerated dose of statins; N = 720 | Percent change in LDL-C from BL to 24 weeks (ITT) | Alirocumab reduced LDL-C by 51 vs. 21 % with ezetimibe (p < 0.0001) | Percentages of pts experiencing at least one tx-emergent AE or serious AEs were comparable between the two groups: 71 and 19 %, respectively (alirocumab) vs. 67 and 18 %, respectively (ezetimibe) |
| ODYSSEY CHOICE I [96] (alirocumab 300 mg every 4 weeks vs. alirocumab 75 mg every 2 weeks [calibrator arm] vs. PL) | Pts with moderate very high CVD risk on maximum tolerated dose of statins; pts with moderate CV risk not receiving statins; pts with moderate to very high CVD risk and statin intolerance; N = 803 | Percentage LDL-C change from BL to week 24 and to averaged LDL-C for weeks 21–24 | Alirocumab 300 mg every 4 weeks mean differences vs. PL were −52 % (pts not receiving statin) and −59 % (pts receiving statins) (p < 0.0001); average reductions to weeks 21–24 were also greater in the alirocumab 300-mg group vs. PL in pts not receiving statins (55 %) and in pts receiving statins (65 %) (p < 0.0001) | TEAEs ranged from 61 to 75 % (PL) and 72 to 78 % with alirocumab 300 mg; higher rate of injection-site reactions with alirocumab 300 mg vs. PL |
| ODYSSEY CHOICE II [97] (alirocumab 150 mg every 4 weeks, alirocumab 75 mg every 2 weeks [calibrator arm] or PL for 24 weeks) | Pts with moderate to very high CV risk and SAMS (inability to tolerate ≥2 statins due to muscle symptoms), or moderate CV risk without SAMS; N = 233 | Percentage change in LDL-C from BL to week 24 | Overall, 63.9 % of pts in the alirocumab 150 mg every 4 weeks arm achieved pre-defined LDL-C target levels at week 24 vs. 1.8 % of PL pts (ITT analysis) | TEAEs occurred in 63.8 and 77.6 % of PL- and alirocumab 150 mg every 4 wk-treated pts, respectively. Muscle symptoms were infrequent; the most common TEAEs were injection-site reactions, arthralgia, headache, and nasopharyngitis |
AE adverse effects, BL baseline, CV cardiovascular, FH familial hypercholesterolemia, HeFH heterozygous familial hypercholesterolemia, HR hazard ratio, ITT intention to treat, LDL-C low-density lipoprotein cholesterol, PL placebo, pt(s) patient(s), SAMS statin-associated muscle symptoms, TEAE treatment-emergent adverse effects, tx treatment