Amgen Posts PCSK9 Results

Amgen has posted results from its 52-week Open Label Study of Long TERm Evaluation Against LDL-C (OSLER) Phase II trial, a safety and efficacy study. The study 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% in combination with SOC in patients with high cholesterol. Data from the first 52-week study of a PCSK9 inhibitor were presented for the first time today in a session at the American Heart Association (AHA) Scientific Sessions 2013 in Dallas and simultaneously published in Circulation.

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.

Adverse events occurred in 81.4% of patients treated with evolocumab and SOC and in 73.1% of the SOC group. The five most common AEs in the evolocumab and SOC group compared to the SOC group were nasopharyngitis (12.2% vs. 9.8%), upper respiratory tract infections (7.7% vs. 7.6%), influenza (7.1% vs. 5.2%), arthralgia (6.9% vs. 4.3%), and back pain (6.5% vs. 5.4%). Other AEs that were reported included muscle-related events (9.2% vs. 9.8%), elevated liver function tests (1.8% vs. 1.6%), and elevated creatine kinase (1.0% vs. 1.9%) for patients treated with evolocumab and SOC compared to SOC alone, respectively. Serious AEs occurred in 7.1% of patients treated with evolocumab and SOC and 6.3% 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% 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% at the end of the parent study vs. 52% at 52 weeks. Improvements in lipoprotein(a) and apolipoprotein B were also sustained up to 52 weeks.

Amgen’s Phase III program for evolocumab involves 13 trials with a combined planned patient enrollment of more than 28,00 patients.