Amgen has reported results from the Open Label Study of Long TERm Evaluation Against LDL-C (OSLER) trial, a long-term controlled 52-week safety and efficacy study, which showed that monthly treatment with evolocumab (AMG 145), an investigational fully human monoclonal antibody that inhibits PCSK9, a protein that reduces the liver's ability to remove low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, from the blood, was not associated with a major increase in adverse events (AEs) versus standard of care (SOC) and produced mean LDL-C reductions of 52 per cent in combination with SOC in patients with high cholesterol.
These data from the first 52-week study of a PCSK9 inhibitor were presented for the first time in a Clinical Science: Special Reports session at the American Heart Association (AHA) Scientific Sessions 2013 in Dallas and simultaneously published in Circulation.
According to the Centres for Disease Control and Prevention, more than 71 million American adults have high LDL-C. Elevated LDL-C is recognized as a major risk factor for cardiovascular (CV) disease, which is the number one cause of death worldwide, claiming more lives each year than cancer, chronic lower respiratory disease and accidents combined.
"Phase II findings from OSLER, the first reported 52-week evaluation of a PCSK9 inhibitor, are encouraging and suggest evolocumab may be a promising option to treat hyperlipidemia in a range of at-risk patients," said Sean E Harper, MD, executive vice president of Research and Development at Amgen. "We look forward to phase III results from our PROFICIO clinical programme evaluating the safety and efficacy of two distinctive dosing options of evolocumab in a range of at-risk patient populations."
OSLER is an ongoing open-label extension study evaluating the long-term safety and efficacy of evolocumab in patients with high cholesterol. In the first year, patients were randomized 2:1 to receive evolocumab and SOC or SOC alone.
"Many patients with high cholesterol struggle to adequately reduce their LDL-C, a significant contributor to cardiovascular disease," said Michael Koren, MD, of the Jacksonville Centre for Clinical Research. "The results from the OSLER study are encouraging as evolocumab may offer a potential treatment option for patients who cannot control their cholesterol levels."
Adverse events occurred in 81.4 per cent of patients treated with evolocumab and SOC and in 73.1 per cent of the SOC group. The five most common AEs in the evolocumab and SOC group compared to the SOC group were nasopharyngitis (12.2 per cent vs. 9.8 per cent), upper respiratory tract infections (7.7 per cent vs. 7.6 per cent), influenza (7.1 per cent vs. 5.2 per cent), arthralgia (6.9 per cent vs. 4.3 per cent), and back pain (6.5 per cent vs. 5.4 per cent). Other AEs that were reported included muscle-related events (9.2 per cent vs. 9.8 per cent), elevated liver function tests (1.8 per cent vs. 1.6 per cent), and elevated creatine kinase (1.0 per cent vs. 1.9 per cent) for patients treated with evolocumab and SOC compared to SOC alone, respectively. Serious AEs occurred in 7.1 per cent of patients treated with evolocumab and SOC and 6.3 per cent of the SOC group.
In the OSLER clinical trial, subcutaneous monthly treatment with evolocumab in combination with SOC resulted in a significant LDL-C decrease versus SOC alone in patients who previously completed one of four 12-week phase II studies of evolocumab. After 52 weeks of treatment, patients who first received evolocumab in the OSLER study experienced an average of 52 per cent reduction in LDL-C, as measured by the accepted standard preparative ultracentrifugation compared to baseline of the phase II parent study. Patients who received one of six dosing regimens of evolocumab in the parent studies and received evolocumab and SOC in OSLER had persistent average LDL-C reductions of 50 per cent at the end of the parent study vs. 52 per cent at 52 weeks. Improvements in lipoprotein(a) and apolipoprotein B were also sustained up to 52 weeks.
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