THOUSAND OAKS, Calif.—Amgen today announced new detailed data from two Phase 3 pivotal studies that showed treatment with its novel investigational cholesterol-lowering medication, evolocumab (AMG 145) resulted in a statistically significant reduction in low-density lipoprotein cholesterol (LDL-C) between 37 and 39 percent, compared to ezetimibe in patients with high cholesterol who cannot tolerate statins (GAUSS-2) and between 55 and 76 percent compared to placebo when used in combination with statin therapy in patients with high cholesterol (LAPLACE-2). Results from the two separate Phase 3 studies, GAUSS-2 and LAPLACE-2, were presented today as Late-Breaking Clinical Trials and complement the three Phase 3 studies presented yesterday as Featured Clinical Research at the American College of Cardiology's 63rd Annual Scientific Session (ACC.14). Positive results from the GAUSS-2 study were simultaneously published in the Journal of the American College of Cardiology.
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.
"As treatment with statins continues to be an important tool in the management of high cholesterol, we are encouraged by the positive data from the Phase 3 studies of evolocumab in patients with statin intolerance and in patients already on statin therapy," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We hope that evolocumab will be able to help patients who are on a moderate or high-intensity statin and not adequately controlled, as well as patients who cannot tolerate statins and are in need of an alternate treatment option to help lower their LDL cholesterol levels.
"Results from the five Phase 3 pivotal studies that we presented at ACC span more than 4,000 patients and provide us with important insights on the potential of evolocumab as a treatment for a range of patients at-risk for cardiovascular disease," Harper added. "We are working closely with regulatory authorities on our global filing plan in hopes of bringing this new treatment option to patients with dyslipidemia."
The GAUSS-2 study showed that in 307 patients with high cholesterol who could not tolerate effective doses of at least two different statins due to muscle-related side effects, treatment with subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly), significantly reduced mean LDL-C by 37 to 39 percent from baseline compared to ezetimibe (p<0.001). Results of the study showed the mean percent reduction from baseline in LDL-C at weeks 10 and 12 were 37 percent for evolocumab 140 mg every two weeks and 39 percent for evolocumab 420 mg monthly compared to ezetimibe. At week 12, the percent reduction from baseline in LDL-C was 38 percent for evolocumab 140 mg every two weeks and 38 percent for evolocumab 420 mg monthly compared to ezetimibe.
"Data from the GAUSS-2 study suggest evolocumab could be a promising lipid-lowering treatment for patients with high cholesterol who cannot tolerate effective doses of statins," said GAUSS-2 lead investigator Erik S.G. Stroes, M.D., chair and professor of the Department of Vascular Medicine at the Academic Medical Center, Amsterdam. "The GAUSS-2 results are encouraging for these patients who are in need of effective lipid-lowering treatment options."
The LAPLACE-2 study showed that in 1,896 patients with high cholesterol (LDL-C >80 mg/dL), treatment with subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) in combination with different daily doses of statin therapy significantly reduced mean LDL-C by 55 to 76 percent from baseline compared to placebo and 38 to 47 percent from baseline compared to ezetimibe (p<0.001). Results of the study showed the mean reduction in LDL-C from baseline at weeks 10 and 12 was between 66 and 75 percent for evolocumab 140 mg every two weeks versus placebo and between 38 and 45 percent versus ezetimibe, for all statin cohorts. Results of the study also showed the mean percent reduction in LDL-C from baseline at weeks 10 and 12 was between 63 and 75 percent for evolocumab 420 mg monthly versus placebo and 44 percent versus ezetimibe, for all statin cohorts.
At week 12, the percent reduction from baseline in LDL-C was between 68 and 76 percent for evolocumab 140 mg every two weeks and between 55 and 71 percent for evolocumab 420 mg monthly, compared to placebo, for all statin cohorts. Compared with ezetimibe, evolocumab reduced LDL-C from baseline between 40 and 47 percent when dosed
"The positive results from the LAPLACE-2 study show that adding evolocumab to statin therapy additionally lowers LDL cholesterol levels when added to moderate or high doses of statins," said LAPLACE-2 lead investigator Jennifer G. Robinson, M.D., M.P.H., director of the Prevention Intervention Center, professor of the Departments of Epidemiology & Medicine, College of Public Health at the University of Iowa. "While statins are effective in reducing LDL cholesterol levels and the risk of heart attack and stroke, some patients still need more LDL- lowering treatment options."
High cholesterol is the most common form of dyslipidemia, which is an abnormality of lipids in the blood. There are approximately 300 million cases of dyslipidemia in the U.S., Japan and Western Europe. According to the Centers for Disease Control and Prevention, more than 71 million American adults have high LDL-C5, or "bad" cholesterol, and elevated LDL-C is recognized as a major risk factor for cardiovascular disease.
Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C cholesterol from the blood. Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.
The Evolocumab Clinical Trial Program PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations, is a large and comprehensive clinical trial program evaluating evolocumab in 20 clinical trials, with a combined planned enrollment of nearly 30,000 patients.
The Phase 3 program includes 14 trials to evaluate evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2 and YUKAWA-2); in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2 and GAUSS-3); as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2); in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2 and TAUSSIG) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia; as well as the administration of evolocumab (THOMAS-1 and THOMAS-2).
Five studies in the evolocumab Phase 3 program will provide long-term safety and efficacy data. These include FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), which will assess whether treatment with evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease; DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) in patients with hyperlipidemia at risk for cardiovascular disease; OSLER-2 (Open Label Study of Long TERm Evaluation Against LDL-C Trial-2) in patients with high cholesterol who completed any of the Phase 3 studies; GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), which will determine the effect of evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization; and TAUSSIG (Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects with Genetic LDL Disorders), which will assess the long-term safety and efficacy of evolocumab on LDL-C in patients with severe familial hypercholesterolemia.
Amgen is dedicated to addressing important scientific questions in order to advance care and improve the lives of patients with cardiovascular disease. Through its own research and development efforts and innovative partnerships, Amgen has built a robust cardiology pipeline consisting of several investigational molecules in an effort to address a number of today's important unmet patient needs, such as high cholesterol and heart failure.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.