Two new sets of trial data of the PROFICIO program have shown positive results for the PCSK9 inhibitor evolocumab. The PROFICIO program stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations, and is a large and comprehensive clinical trial program evaluating evolocumab.
Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C from the blood.

In the Phase 3 LAPLACE-2 (LDL-C Assessment with PCSK9 MonoclonaLAntibody Inhibition Combined with Statin ThErapy-2) trial, that evaluated evolocumab in combination with statin therapy in patients with high cholesterol, the co-primary endpoints were met: 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.
In 1896 patients with high cholesterol, safety, tolerability and efficacy of subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) in combination with statin therapy was compared to placebo and ezetimibe. Safety was similar between the different treatment groups. There were no adverse events that occurred in more than 2% of the evolocumab-combined group.
Adding evolocumab to statin therapy may thus help patients to control their LDL-c levels when high doses of statins are not sufficient.

The Phase 3 RUTHERFORD-2 (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2) trial is the fifth trial in the phase 3 program, and evaluated evolocumab in combination with statins and other lipid-lowering therapies in patients with heterozygous familial hypercholesterolemia (HeFH). In RUTHERFORD-2 the co-primary endpoints were met, namely 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.
In this trial, 329 HeFH patients were randomised 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), while they were on a stable dose of statin and other lipid-lowering therapies.
Some adverse events were more often seen with evolocumab (>2% in evolocumab combined group and >2% compared to placebo), namely nasopharyngytis, contusion, back pain, nausea, influenza and myalgia.
These data suggest that evolocumab may therefore offer a new treatment option as an add-on therapy to existing lipid-lowering medication, in patients with heterozygous familial hypercholesterolaemia.

Sean Harper, M.D. and executive vice president of Research and Development at Amgen concludes in a press release “The robust data from these five studies in the phase 3 program will form the basis of our global filing plan and we look forward to discussions with regulatory agencies.” In addition, five studies of evolocumab will provide long-term safety and efficacy data, in different treatment combinations and different patient populations.
 Amgen press releases 28 January, 2014 and 30 January, 2014