Amgen, a company that discovers, develops, manufactures and delivers innovative human therapeutics, has reported positive results from phase I b 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 per cent 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.

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, MD, executive vice president of Research and Development at Amgen. “Based on these results, Amgen initiated a robust phase II programme 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 I b 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 per cent 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 per cent 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 per cent 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 per cent] AMG 145 versus 1 [7 per cent] placebo), injection site haematoma (2 [5 per cent] AMG 145 versus 2 [14 per cent] placebo), and viral upper respiratory tract infection (2 [5 per cent] AMG 145 versus 1 [7 per cent] placebo).

AMG 145 is a 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 causing bad cholesterol to increase. AMG 145, developed by Amgen scientists, binds to PCSK9 circulating in the blood and prevents PCSK9 from binding to LDL receptors in the liver. Without PCSK9 bound to them, the LDL receptors can take up and remove LDL-C from the blood, recycle and remain available for binding additional LDL-C.

Amgen is currently conducting a phase II programme for AMG 145 that will enroll approximately 1,900 patients across six studies to evaluate the effects of AMG 145 across multiple patient populations who may benefit from additional cholesterol lowering treatment options. The phase II programme is evaluating AMG 145 in combination with statins in patients with or at risk for cardiovascular disease, in patients who cannot tolerate statins, as a stand-alone treatment in patients with low cardiovascular risk, and in patients whose cholesterol is caused by a genetic disorder called heterozygous familial hypercholesterolemia.