OBJECTIVES: This study sought to evaluate the efficacy and safety of 
subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic 
patients who are unable to tolerate effective statin doses.
BACKGROUND: Statin intolerance, which is predominantly due to muscle-related 
side effects, is reported in up to 10% to 20% of patients. Evolocumab, a fully 
human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 
(PCSK9), demonstrated marked reductions in plasma low-density lipoprotein 
cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients.
METHODS: The GAUSS-2 (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in 
Statin Intolerant Subjects) trial was a 12-week, double-blind study of 
randomized patients (2:2:1:1) to evolocumab 140 mg every two weeks (Q2W) or 
evolocumab 420 mg once monthly (QM) both with daily oral placebo or subcutaneous 
placebo Q2W or QM both with daily oral ezetimibe 10 mg. Co-primary endpoints 
were percent change from baseline in LDL-C at the mean of weeks 10 and 12, and 
at week 12.
RESULTS: Three hundred seven patients (age 62 ± 10 years; LDL-C 193 ± 59 mg/dl) 
were randomized. Evolocumab reduced LDL-C from baseline by 53% to 56%, 
corresponding to treatment differences versus ezetimibe of 37% to 39% 
(p <0.001). Muscle adverse events occurred in 12% of evolocumab-treated patients 
and 23% of ezetimibe-treated patients. Treatment-emergent adverse events and 
laboratory abnormalities were comparable across treatment groups.
CONCLUSIONS: Robust efficacy combined with favorable tolerability makes 
evolocumab a promising therapy for addressing the largely unmet clinical need in 
high-risk patients with elevated cholesterol who are statin intolerant. (Goal 
Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant 
Subjects-2; NCT01763905).