At the American College of Cardiology’s 63rd Annual Scientific Session, Amgen announced late-breaking results from two Phase III trials. One trial indicated that Amgen’s evolocumab reduced low-density lipoprotein cholesterol (LDL-C) cholesterol in statin-resistant patients. Another trial showed the drug reduced LDL-C in patients already receiving statin therapy. These results, together with data from three additional Phase III trials presented earlier at the session, span more than 4,000 patients with dyslipidemia and form the basis of Amgen’s global filing plan.
All five trials demonstrate the potential of Amgen’s evolocumab (AMG 145), 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 or “bad” cholesterol from the blood. Evolocumab 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.
In one of the late-breaking trials, GAUSS-2 (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2), treatment with subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) significantly reduced mean LDL-C by 37–39% from baseline compared to ezetimibe in 307 patients with high cholesterol who could not tolerate effective doses of at least two different statins due to muscle-related side effects.
In the other late-breaking trial, LAPLACE-2 (LDL-C Assessment with PCSK9 MonoclonaL Antibody Inhibition Combined with Statin ThErapy-2), 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 55–76% from baseline compared to placebo and 38–47% from baseline compared to ezetimibe. This trial included 1,896 patients with high cholesterol (LDL-C > 80 mg/dL).
“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 III 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-C levels.”
“We are working closely with regulatory authorities on our global filing plan in hopes of bringing this new treatment option to patients with dyslipidemia,” Harper added. Dyslipidemia most commonly manifests as high cholesterol. There are approximately 300 million cases of dyslipidemia in the United States, Japan, and Western Europe. According to the Centers for Disease Control and Prevention, more than 71 million American adults have high LDL-C, or “bad” cholesterol, and elevated LDL-C is recognized as a major risk factor for cardiovascular disease.
The late-breaking trials discussed at the meeting of the American College of Cardiology are parts of PROFICIO, a broad evaluation program. PROFICIO stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different Populations. It is evaluating evolocumab in 20 clinical trials, with a combined planned enrollment of nearly 30,000 patients.