Amgen has announced that the Phase 3 RUTHERFORD-2 ( RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2 ) trial evaluating Evolocumab in combination with statins and other lipid-lowering therapies in patients with heterozygous familial hypercholesterolemia ( HeFH ) met its co-primary endpoints: the percent reduction from baseline in low-density lipoprotein cholesterol ( LDL-C ) at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. The mean percent reductions in LDL-C were consistent with the results observed for the same doses in the Phase 2 RUTHERFORD trial for Evolocumab compared to placebo.
Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), a protein that reduces the liver's ability to remove LDL-C from the blood.
The RUTHERFORD-2 trial has evaluated safety, tolerability and efficacy of Evolocumab in 329 heterozygous familial hypercholesterolemia ( LDL-C greater than100 mg/dL ) patients on a stable dose of statin and other lipid-lowering therapies.
Patients were randomized to one of four treatment groups to compare subcutaneous Evolocumab ( 140 mg every two weeks or 420 mg monthly ) with subcutaneous placebo ( every two weeks or monthly ).
The co-primary endpoints were the percent reduction from baseline in LDL-C at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: absolute change from baseline in LDL-C; LDL-C less than 70 mg/dL; and the percentage change from baseline in non-high-density lipoprotein cholesterol ( non-HDL-C ), apolipoprotein B ( ApoB ), total cholesterol (TC)/HDL-C ratio, ApoB/apolipoprotein A1 ( ApoA1 ) ratio, lipoprotein(a), triglycerides, HDL-C and very low-density lipoprotein cholesterol ( VLDL-C ).
Safety was balanced across treatment groups except for the following most common adverse events ( greater than or equal to 2% in Evolocumab combined group and greater than or equal to 2% compared to placebo ): nasopharyngitis ( 8.6% Evolocumab; 4.6% placebo ), contusion ( 4.1% Evolocumab; 0.9% placebo ), back pain ( 3.6% Evolocumab; 0.9% placebo ), nausea ( 3.6% Evolocumab; 0.9% placebo ), influenza ( 3.2% Evolocumab; 0.0% placebo ), and myalgia ( 2.7% Evolocumab; 0.0% placebo ). ( Xagena )
Source: Amgen, 2014