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. 2016 Jun 21;57(1):7–32. doi: 10.1002/jcph.766

Table 3.

Change in Non‐LDL‐C Lipids Reported to Date in Phase 2 and Phase 3 Clinical Trials of PCSK9‐Specific Antibodies: Trials Reporting These Parameters to Date

Change From Baseline to Primary Endpoint, %
Trial BG Therapy Treatment Comparator Lp(a) (Median) TC (LSM) HDL‐C (LSM) Non‐HDL‐C (LSM) Apo B (LSM) Apo A1 (LSM) TG (Median) VLDL‐C (LSM) TC/HDL‐C Ratio (LSM) Apo B/apo A1 Ratio (LSM)
Heterozygous familial hypercholesterolemia
Stein 201268 N = 77 Statin ± EZE Aliroc Placebo −23.38 to −7.45 vs −3.91 −43.55 to −18.10 vs −8.48 +6.49 to +12.34 vs +2.20 −57.90 to −26.84 vs −11.34 −50.19 to −20.91 vs −6.39 +1.69 to +8.82 vs −5.32 −16.73 to −4.92 vs −10.55 NR NR NR
Stein 201467 N = 58 LMT Aliroc OLE −24.5 NR +4.5 NR −45.5 +7.6 NR NR NR NR
ODYSSEY FH I54 N = 486 Max tolerated statin ± other LMT Aliroc Placebo −25.2 vs −7.5a NR +8.8 vs +0.8 −42.8 vs +9.6 −41.1 vs +4.7 +5.0 vs +0.3 −9.6 vs +6.3a NR NR NR
ODYSSEY FH II54 N = 249 Max tolerated statin ± other LMT Aliroc Placebo −30.3 vs −10.0a NR +6.0 vs −0.8 −42.6 vs +3.1 −42.8 vs −3.5 +2.8 vs −1.6 −10.4 vs +0.5a NR NR NR
RUTHERFORD60 N = 168 Statin ± EZE Evo Placebo −27.4 to −19.1 vs +4.1a −37.4 to −28.1 vs +2.9 +9.1 to +10.1 vs +2.3 −51.0 to −39.3 vs +2.5 −43.3 to −31.9 vs +2.9 +10.3 to +10.6 vs +8.6 −10.5 to −5.6 vs +9.4a −18.6 to −7.8 vs +17.0 −42.0 to −33.7 vs +3.0 −48.7 to −38.0 vs −4.1
RUTHERFORD‐262 N = 331 Statin ± LMT Evo Placebo −22.9 to −21.6 vs +6.7 to +8.7 NR +5.4 to +8.1 vs −3.7 to −1.2 −56.2 to −49.7 vs −1.4 to +5.3 −49.8 to −44.8 vs −0.7 to +4.6 +5.7 to +7.3 vs −1.4 to +1.8 −16.1 to −5.1 vs +3.5 to +6.4 NR −46.0 to −38.3 vs +0.1 to +7.1 −52.7 to −45.3 vs +1.5 to +4.2
Hypercholesterolemia and high cardiovascular risk
ODYSSEY COMBO I74 N = 316 Max tolerated statin ± LMT Aliroc Placebo −20.5 vs −5.9 −27.9 vs −2.9 +3.5 vs −3.8 −39.1 vs −1.6 −36.7 vs −0.9 NR −6.0 vs −5.4 NR NR NR
ODYSSEY COMBO II73 N = 720 Max‐ tolerated statin Aliroc Placebo + EZE −27.8 vs −6.1 −29.3 vs −14.6 +8.6 vs +0.5 −42.1 vs −19.2 −40.7 vs −18.3 +5.0 vs −1.3 −13.0 vs −12.8 NR NR NR
Additional patient populations
TESLA69 N = 8 HoFH Diet + LMT Evo Open label −18.6 to −11.7 NR −1.4 to +4.7a NR −14.9 to −12.5a +1.3 to +5.2a −5.7 to +5.8a NR NR NR
TESLA Part B61 N = 50 HoFH Diet + LMT Evo Placebo −9.4 vs +2.4a, b −18.9 vs +7.8 +4.0 vs +4.1 −22.0 vs +8.1 −19.2 vs +4.0 NR −1.4 vs −1.7 +18.7 vs +62.6 −21.6 vs +4.4 −22.5 vs +5.3
Additional patient populations (continued)
ODYSSEY ALTERNATIVE59 N = 361 SI LMT Aliroc EZE −25.9 vs −7.3c −31.8 vs −10.9c +7.7 vs +6.8c, d −40.2 vs −14.6c −36.3 vs −11.2c +4.8 vs +2.9c, d −9.3 vs −3.6c, d NR NR NR
GAUSS71 N = 160 SI Low‐dose statin or LMT Evo Placebo + EZE −25.9 to −20.3 vs −7.9a −37.7 to −29.8 vs −10.7 +5.5 to +7.4 vs −1.1 −48.6 to −39.8 vs −15.0 −42.1 to −33.6 vs −12.2 +6.0 to +7.5 vs −1.4 −19.3 to −14.2 vs −5.5 −28.8 to −15.0 vs −13.2 −40.6 to −32.0 vs −9.6 −45.4 to −36.5 vs −11.4
Evo + EZE Placebo + EZE −29.1 vs −7.9a −44.3 vs −10.7 +12.0 vs −1.1 −59.8 vs −15.0 −49.1 vs −12.2 +8.3 vs −1.4 −9.5 vs −5.5 −37.8 vs −13.2 −49.4 vs −9.6 −52.0 vs −11.4
GAUSS‐270 N = 307 SI Low‐dose statin or LMT Evo Placebo + EZE −27.0 to −22.1 vs −1.7 to +5.8a NR +5.3 to +6.5 vs +1.6 to +1.8 −48.6 to −46.2 vs −16.5 to −13.2 −45.8 to −43.1 vs −13.0 to −10.0 +5.2 to +5.5 vs +1.1 to +3.3 −3.9 to −2.5 vs −5.5 to +2.16 −6.2 to −2.2 vs −5.5 to −2.3 −40.4 to −38.6 vs −14.1 to −9.92 −47.7 to −45.5 vs −13.1 to −11.4
ODYSSEY OPTIONS I76 N = 355 Patients with subtherapeutic response to statins ATV 20 mg or 40 mg ± LMT Aliroc + ATV 20 mg EZE double statin −23.6 vs −10.6 (EZE) and −20.2 (ATV 40 mg) NR +4.8 vs −0.1 (EZE) and +1.9 (ATV 40 mg) −36.7 vs −15.1 (EZE) and −6.3 (ATV 40 mg) −33.7 vs −10.1 (EZE) and −4.4 (ATV 40 mg) NR −12.0 vs −3.3 (EZE) and −6.7 (ATV 40 mg)a NR NR NR
Aliroc + ATV 40 mg EZE double statin −30.8 vs +0.2 (EZE) and −9.7 (ATV 80 mg) and −4.9 (ROS 40 mg) NR +7.7 vs +2.0 (EZE) and +4.7 (ATV 80 mg) and +5.7 (ROS 40 mg) −47.6 vs −21.0 (EZE) and −6.5 (ATV 80 mg) and −17.4 (ROS 40 mg) −41.9 vs −14.3 (EZE) and −3.5 (ATV 80 mg) and −10.9 (ROS 40 mg) NR −19.1 vs −13.9 (EZE) and −7.3 (ATV 80 mg) and −0.5 (ROS 40 mg)a NR NR NR
ODYSSEY OPTIONS II77 N = 305 ROS 10 mg or 20 mg ± LMT Aliroc + ROS 10 mg EZE double statin −27.9 vs −4.3 (EZE) and −4.0 (ROS 20 mg)a NR +9.1 vs +4.0 (EZE) and +1.7 (ROS 20 mg) −42.7 vs −13.4 (EZE) and −11.3 (ROS 20 mg) −36.5 vs −9.7 (EZE) and −7.3 (ROS 20 mg) NR −11.2 vs −8.3 (EZE) and −1.8 (ROS 20 mg)a NR NR NR
Aliroc + ROS 20 mg EZE double statin −22.7 vs −5.8 (EZE) and −5.2 (ROS 40 mg)a NR +7.2 vs −1.8 (EZE) and +1.5 (ROS 40 mg) −31.4 vs −12.9 (EZE) and −11.2 (ROS 40 mg) −28.3 vs −11.2 (EZE) and −9.8 (ROS 40 mg) NR −8.7 vs −11.1 (EZE) and −9.9 (ROS 40 mg)a NR NR NR
Additional patient populations (continued)
Roth 201265 N = 92 Hypercholesterolemia None Aliroc + ATV 10 mg Placebo + ATV 80 mg −34.7 vs −2.7 −40.5 vs −16.6e +2.6 vs −3.6 −58.3 vs −22.3e −54.4 vs −12.0e +0.4 vs −5.2 −4.0 vs −11.9 NR NR NR
Aliroc + ATV 80 mg Placebo + ATV 80 mg −31.0 vs −2.7 −47.2 vs ‐16.6e +5.8 vs −3.6 −63.9 vs −22.3e −58.0 vs −12.0e −2.2 vs −5.2 −24.7 vs −11.9 NR NR NR
McKenney 201258 N = 183 Hypercholesterolemia ATV 10, 20, or 40 mg Aliroc Placebo −28.6 to −7.9 vs 0.0 −45.2 to −23.0 vs −1.6 +4.1 to +8.5 vs −1.0 −62.5 to −33.6 vs −2.2 −56.1 to −27.3 vs +2.2 +0.3 to +4.2 vs 0.0e −18.9 to −5.5 vs +9.7 NR NR NR
ODYSSEY MONO66 N = 103 Hypercholesterolemia; no background LMT None Aliroc Placebo + EZE −16.7 vs −12.3a , f −29.6 vs −10.9 +6.0 vs +1.6 −40.6 vs −15.1 −36.7 vs −11.0 +4.7 vs −0.6 −11.9 vs −10.8f NR NR NR
MENDEL57 N = 411 Hypercholesterolemia None Evo Placebo −27.3 to −9.1 vs +2.0 to +9.2a −34.0 to −26.7 vs −2.2 to +1.4 +5.3 to +11.5 vs +1.1 to +5.7 −48.0 to −37.9 vs −2.9 to −0.3 −44.5 to −32.7 vs −0.3 to +0.2 +1.2 to +9.0 vs −1.6 to +0.7 −10.6 to −5.9 vs −4.2 to +1.4 −26.0 to −10.3 vs −0.1 to +9.8 −40.0 to −30.1 vs −3.4 to −1.2 −48.1 to −32.8 vs +0.1 to +2.0
LAPLACE‐TIMI 5785 N = 631 Hypercholesterolemia Statin ± EZE Evo Placebo NR −42.5 to −26.2g +1.6 to +8.1g −61.4 to −37.8g −56.4 to −34.4g +0.31 to +4.8g −33.7 to −13.4g −44.3 to −21.1g −47.7 to −27.7g −53.4 to −33.8g
OSLER‐155 N = 1104 Hypercholesterolemia ± Statin Evo + SOC Open label −32.8 for no Evo/Evo vs −11.1 for no Evo/SOC and −8.7 for Evo/ SOC −32.5 for no Evo/Evo vs −0.5 for no Evo/SOC and −1.5 Evo/SOCc +8.5 for no Evo/Evo vs +3.5 for no Evo/SOC and +3.7 for Evo/SOCc −45.9 for no Evo/Evo vs −1.2 no Evo/ SOC and −2.8 Evo/ SOCc −42.1 for no Evo/Evo vs −4.2 for no Evo/ SOC and −3.6 for Evo/SOCc +3.6 for no Evo/Evo vs +0.9 for no Evo/ SOC and +0.1 for Evo/ SOCc −8.3 for no Evo/Evo vs +3.7 for no Evo/SOC and −1.4 for Evo/SOCe −14.7 no Evo/Evo vs +11.6 no Evo/ SOC and −4.2 Evo/SOCe −36.9 no Evo/Evo vs −2.3 no Evo/ SOC and −3.1 Evo/ SOCc −43.7 no Evo/Evo vs −4.2 no Evo/SOC and −2.5 Evo/SOCc
SOC Open label −29.9 for Evo/Evo vs −11.1 for no Evo/SOC and −8.7 for Evo/ SOC −33.0 for Evo/Evo vs −0.5 for no Evo/ SOC and −1.5 for Evo/ SOCc +9.1 for Evo/Evo vs +3.5 for no Evo/SOC and +3.7 for Evo/SOCc −46.5 vs −1.2 and −2.8c −42.6 for Evo/Evo vs −4.2 for no Evo/SOC and −3.6 for Evo/SOCc +4.9 for Evo/Evo vs +0.9 for no Evo/SOC and +0.1 for Evo/SOCc −9.0 for Evo/Evo vs +3.7 for no Evo/SOC and −1.4 for Evo/SOCe −18.8 for Evo/Evo vs +11.6 for no Evo/SOC and −4.2 for Evo/ SOCe −37.5 for Evo/Evo vs −2.3 for no Evo/SOC and −3.1 for Evo/SOCc −44.7 for Evo/Evo vs −4.2 for no Evo/SOC and −2.5 for Evo/SOCc
Additional patient populations (continued)
OSLER‐1/OSLER‐275 , h N = 4465 Hypercholesterolemia SOC Evo Open label −25.5 vs 0.0 −32.3 vs +3.8c +8.7 vs +1.7c −46.1 vs +5.9c −41.7 vs +5.5c +6.8 vs +2.6c −9.1 vs +3.5 NR NR NR
DESCARTES51 N = 905 Hypercholesterolemia Diet + none; diet + ATV Evo + diet Placebo −22.5 vs −12.8a −30.9 vs +5.4 +9.2 vs −2.1 −44.9 vs +9.5 −43.3 vs −0.4 +3.1 vs −1.7 −7.7 vs +15.4a −2.1 vs +77.2 −34.7 vs +9.7 −44.1 vs +1.9c
Diet + ATV + EZE Evo + diet + ATV 10 mg Placebo −32.8 vs −3.6a −30.1 vs +5.3 +4.8 vs −0.5 −46.0 vs +8.5 −44.8 vs +2.9 +1.5 vs −0.9 −1.0 vs +10.2a +8.6 vs +28.7 −32.1 vs +6.8 −45.1 vs +4.4c
Evo + diet + ATV 80 mg Placebo −30.1 vs −10.6a −25.0 vs +8.1 +5.4 vs +1.5 −37.8 vs +11.7 −39.2 vs +5.4 +3.4 vs −0.1 −0.9 vs +11.5a +4.4 vs +35.5 −28 vs +8.4 −40.8 vs +6.1c
Evo + diet + ATV 80 mg + EZE Placebo −20.5 vs −1.1a −27.0 vs +1.7 +5.0 vs +1.0 −38.9 vs +2.4 −37 vs +0.8 +0.9 vs −1.7 −2.1 vs +1.6a −3.9 vs +13.6 −28.8 vs +2.2 −36.2 vs +2.9c
MENDEL‐256 N = 614 Hypercholesterolemia None Evo Placebo −20.4 to −17.8 vs 0.0e NR +4.1 to +4.8 vs −5.3 to −1.2e −50.1 to −49.7 vs −0.3 to +1.5 −47.2 to −46.6 vs +0.6 to +1.8 NR −15.6 to −8.1 vs −1.9 to +2.0 −16.3 to −9.5 vs −1.6 to 0.0e NR −48.5 to −48.3 vs +1.1 to +4.5
EZE −2.1 to 0.0e NR −2.8 to −1.5e −16.5 to −14.9 −14.0 to −13.2 NR −2.4 to 0.0 −3.6 to −0.9e NR −14.3 to −12.7
LAPLACE‐263 , i N = 1899 Hypercholesterolemia ATV 10 mg Evo Placebo −25.9 to −20.3 vs −0.4 to +7.3a −37.2 to −36.5 vs +1.4 to +5.6 +7.0 to +7.9 vs 0.0 to +0.2 −53.4 to −52.5 vs +2.4 to +8.3 −50.9 to −47.15 vs +0.21 to +7.89 NR −13.3 to −3.8 vs +8.3 to +14.4a −11.7 to −6.2 vs +8.3 to +14.7 NR NR
EZE +3.3 to +7.2a −14.3 to −11.3 −1.8 to −0.4 −18.27 to −14.8 −15.98 to −10.95 NR −0.4 to +4.9a −4.6 to +3.5 NR NR
ATV 80 mg Evo Placebo −24.7 to −24.6 vs −2.2 to +3.4a −36.3 to −32.6 vs +6.0 to +9.34 +7.4 to +9.1 vs +0.3 to +5.0 −54.8 to −50.1 vs +10.0 to +11.8 −49.77 to −46.47 vs +6.54 to +11.64 NR −10.1 to −1.1 vs +6.7 to +8.2a −9.7 to −1.1 vs +6.7 to +8.5 NR NR
EZE +8.0 to +10.2a −12.3 to −10.0 +0.2 to +0.6 −17.3 to −14.3 −12.31 to −12.16 NR −7.4 to −3.1a −7.9 to −6.0 NR NR
SIM 40 mg Evo Placebo −38.06 to −29.23 vs −6.81 to −1.06a −41.9 to −36.5 vs +0.4 to +0.7 +6.4 to +10.9 vs −2.7 to +1.1 −59.02 to −50.96 vs +1.89 to +5.66 −55.95 to −49.16 vs +0.35 to +3.57 NR −14.7 to −13.7 vs +8.1 to +16.7a −15.9 to −14.8 vs +7.6 to +21.0 NR NR
Additional patient populations (continued)
ROS 5 mg Evo Placebo −25.09 to −20.85 vs +4.49 to +11.40a −36.4 to −36.3 vs +3.1 to +6.3 +6.1 to +7.2 vs −0.2 to +2.9 −52.04 to −51.57 vs +5.85 to +7.92 −50.15 to −48.58 vs +4.63 to +6.35 NR −6.9 to −4.5 vs +13.0 to +13.6a −8.2 to −6.3 vs +12.5 to +13.8 NR NR
ROS 40 mg Evo Placebo −26.11 to −21.97 vs +10.21 to +10.38a −33.3 to −29.8 vs +1.2 vs +4.3 +4.7 to +5.6 vs −0.4 to +0.7 −50.97 to −46.42 vs +3.35 to +8.61 −45.61 to −43.71 vs +3.24 to +4.91 NR −10.5 to +5.6 vs +10.0 to +11.0a −10.0 to −6.1 vs +8.6 to +10.1 NR NR
Ballantyne 201572 N = 354 Hypercholesterolemia Statin Boco Placebo −10.7 to 0.0 vs 0.0 to +3.5 −31.6 to −10.5 vs −2.4 to +1.2c +2.7 to +7.1 vs −0.4 to +0.8c −44.9 to −17.3 vs −2.3 to +2.8c −37.4 to −13.6 vs −2.1 to +1.5c +2.9 to +9.9 vs +1.8 to +2.1c −18.6 to −7.6 vs −14.5 to +3.7 NR NR NR
ODYSSEY LONG TERM64 N = 2341 HeFH, or high CV risk Max‐tolerated statin ± other LMT Aliroc Placebo −30.2 vs −3.9 −38.8 vs −0.4 +4.2 vs −0.7 −53.1 vs +0.6 −54.3 vs +1.2 +4.2 vs +1.2 −15.8 vs +1.4 NR NR NR

Aliroc, alirocumab; apo A1, apolipoprotein A1; apo B, apolipoprotein B; ATV, atorvastatin; BG, background; Boco, bococizumab; CV, cardiovascular; Evo, evolocumab; EZE, ezetimibe; HDL‐C, high‐density lipoprotein cholesterol; HeFH, heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; LDL‐C, low‐density lipoprotein cholesterol; LMT, lipid‐modifying therapy; Lp(a), lipoprotein(a); LSM, least squares mean; NR, not reported; OLE, open‐label extension; ROS, rosuvastatin; SI, statin intolerance; SIM, simvastatin; SOC, standard of care; TC, total cholesterol; TG, triglycerides; VLDL‐C, very low‐density lipoprotein cholesterol.

a

LSM.

b

Multiplicity adjustments following the Hochberg procedure were used to control for overall significance at the 0.05 level of significance for the primary and secondary endpoints.

c

Mean change from baseline.

d

Hierarchical testing terminated at the endpoint of HDL‐C (baseline to week 24, intention‐to‐treat analysis), and this statistical comparison and all subsequent comparisons (TG and apo A1) were not considered statistically significant.

e

Median.

f

Combined estimate for adjusted mean (SE) percentage changes are shown.

g

Mean change vs placebo.

h

Change at 12 weeks in OSLER program (including OSLER‐1 and OSLER‐2).

i

Similar results were observed for the mean of weeks 10 and 12.