Table 2.
Summary of results from evolocumab trials in patient groups with unmet needs
| Study | Population | Primary endpoints | Efficacy | Safety |
|---|---|---|---|---|
| GAUSS-2 [79] (evolocumab vs. ezetimibe) | Pts with hyperlipidemia who cannot tolerate statin therapy; N = 307 | Percent change from BL in LDL-C level at the mean of weeks 10 and 12, and at week 12 | Evolocumab reduced LDL-C from BL by 53–56 %: tx differences vs. ezetimibe of 37–39 % (p < 0.001) | Muscle AEs: 12 % of evolocumab-treated pts vs. 23 % of ezetimibe-treated pts; TEAEs and laboratory abnormalities comparable across tx groups |
| RUTHERFORD-2 [80] (evolocumab vs. PL) | Pts with HeFH, on stable lipid-lowering therapy; N = 329 | Percent change from BL in LDL-C level at the mean of weeks 10 and 12, and at week 12 | Evolocumab reduced mean LDL-C at week 12 (every-2-week dose: 59 % reduction, monthly dose: 61 % reduction; both p < 0.0001) and at the mean of week 10 and 12 (60 % reduction and 66 % reduction; both p < 0.0001) | Similar rates of AEs in both groups, except for nasopharyngitis (19 pts [9 %] in the evolocumab group vs. 5 [5 %] in the PL group) and muscle-related AEs (10 pts [5 %] in the evolocumab group vs. 1 [1 %] in the PL group) |
| TESLA [81] (evolocumab vs. PL) | Pts with HoFH, on stable lipid-lowering therapy; N = 49 | Percentage change from BL in ultracentrifugation LDL-C level at week 12 | Evolocumab reduced ultracentrifugation LDL-C at 12 weeks by 31 % (p < 0.0001) | TEAEs occurred in 10 (63 %) of 16 pts in the PL group and 12 (36 %) of 33 in the evolocumab group |
| DESCARTES [82] (evolocumab vs. PL) | Pts with hyperlipidemia and a wide range of CV risk, after a run-in period of background lipid-lowering therapy; N = 901 | Percent change from BL in ultracentrifugation LDL-C level at week 52 | Overall LSM (±SE) reduction in LDL-C 57 ± 2 % (taking into account reduction in PL group) (p < 0.001); mean reduction 56 ± 4 % in pts with diet alone as background therapy, 62 ± 3 % with atorvastatin 10 mg, 57 ± 5 % with atorvastatin 80 mg, and 49 ± 5 % with combination of atorvastatin 80 mg and ezetimibe 10 mg (p < 0.001 for all comparisons) | Overall incidence of AE occurring during tx was similar in the evolocumab and PL groups: 448 of 599 pts (75 %) vs. 224 of 302 pts (74 %); most common AEs in the evolocumab group: nasopharyngitis, URTI, influenza, and back pain |
| LAPLACE-2 [83] (evolocumab vs. ezetimibe and PL) | Pts at risk for CVD receiving statin therapy; N = 1899 | Percent change from BL in LDL-C level at mean of weeks 10 and 12 and at week 12 | Evolocumab reduced LDL-C levels by 66–75 % (every 2 weeks) and by 63–75 % (monthly) vs. PL at mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups; LDL-C reductions at week 12 were comparable | AEs reported in 36 %, 40 %, and 39 % of evolocumab-, ezetimibe-, and PL-treated pts, respectively; most common AEs in evolocumab-treated pts were back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2 %) |
| TAUSSIG [84] (evolocumab long-term open-label; interim results; estimated completion, January 2020) | Pts with HoFH, receiving stable lipid-lowering therapy; N = 100 (non-apheresis, N = 66; apheresis, N = 34) | Percentage change from BL in LDL-C at week 12 | Evolocumab reduced LDL-C in the overall cohort by 21 % (p < 0.05); reduction maintained in the longer-term (up to 48 weeks); in a subset of non-apheresis pts, who uptitrated to 420 mg every 2 weeks (N = 28), LDL-C was reduced by a further 6 % (p = 0.01) | Evolocumab was well-tolerated |
AE adverse effect, BL baseline, CV cardiovascular, CVD cardiovascular disease, HeFH heterozygous familial hypercholesterolaemia, HoFH homozygous familial hypercholesterolaemia, LDL-C low-density lipoprotein cholesterol, LSM least squares mean, PL placebo, pt(s) patient(s), SE standard error, TEAE treatment-emergent adverse effect, tx treatment, URTI upper respiratory tract infection