Amgen (NASDAQ: AMGN) announced today positive results from a Phase 1b clinical study of AMG 145, an investigational PCSK9 inhibitor, in patients with high cholesterol who were taking statins. The study demonstrated that multiple doses of AMG 145 significantly reduced serum low density lipoprotein cholesterol (LDL-C), also known as "bad" cholesterol, by up to 81 percent versus placebo (maximum reduction) in subjects on low to moderate doses of statins (p
<0.001). The cholesterol lowering effects of AMG 145 were similar among patients on high doses of statins (80 mg atorvastatin and 40 mg rosuvastatin) and patients on low to moderate doses of statins. No deaths or serious adverse events (AEs) were reported in the study. Full results of the study were presented for the first time today in an oral session at the American College of Cardiology Scientific Session in Chicago. (Abstract # 923-4)
High LDL cholesterol (LDL-C) is a major public health issue in most countries as it contributes to the risk of developing cardiovascular disease, the leading cause of death among men and women. Most patients who are treated for high cholesterol take drugs known as statins. While statins are effective, many patients still have difficulty reaching their cholesterol goals and others cannot tolerate statin therapy. AMG 145 is a fully human monoclonal antibody that inhibits PCSK9, a protein that reduces the liver's ability to remove LDL-C from the blood.
"Early studies have shown that AMG 145 lowers levels of PCSK9 in the body and brings LDL-cholesterol levels down as a result," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Based on these results, Amgen initiated a robust Phase 2 program that will provide a deeper understanding of the benefit-risk profile of inhibiting PCSK9 in a wide variety of patients whose high cholesterol cannot be controlled with existing therapies. We look forward to seeing the results of these studies later this year."
The Phase 1b study of 51 patients on stable doses of statins was designed to assess the safety and tolerability of AMG 145 and its effect on LDL-C levels versus placebo. Patients on low to moderate doses of statins who received AMG 145 every two weeks had mean LDL-C reductions of up to 75 percent versus placebo at week six (three subcutaneous doses). The patients on low to moderate doses of statins who received AMG 145 every four weeks demonstrated up to a 66 percent reduction in LDL-C at week eight (two subcutaneous doses). The magnitude and duration of effect were dose-dependent. Plasma PCSK9 was undetectable at higher doses. Patients on high doses of statins who received AMG 145 every two weeks had a mean reduction in LDL-C of up to 63 percent versus placebo at week six (three subcutaneous doses).
AE profiles were similar for AMG 145 and placebo with the most common AEs observed encompassing nasopharyngitis (3 [7 percent] AMG 145 versus 1 [7 percent] placebo), injection site hematoma (2 [5 percent] AMG 145 versus 2 [14 percent] placebo), and viral upper respiratory tract infection (2 [5 percent] AMG 145 versus 1 [7 percent] placebo).