For patients who tolerate only lowest-strength statin doses or nonstatin lipid-lowering therapies, alirocumab 150 mg every 4 weeks helped achieve robust low-density lipoprotein cholesterol (LDL-C) reduction and was tolerated in the long-term, according to a study published in the Journal of Cardiology.
The investigators of this double-blind study sought to evaluate the efficacy of alirocumab 150 mg administered every 4 weeks (Q4W) in addition to receiving background lowest-dose statin or nonstatin lipid-lowering therapy to reduce LDL-C levels and the long-term safety of open-label alirocumab treatment in Japanese patients with hypercholesterolemia.
The study population was 163 patients enrolled in the ODYSSEY NIPPON study (ClinicalTrials.gov Identifier: NCT02584504) across 30 sites in Japan. All patients were diagnosed with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia and were on atorvastatin 5 mg/day or nonstatin lipid-lowering therapy and had not met the recommended LDL-C levels.
Participants were stratified according to background statin or nonstatin use and were randomized to receive subcutaneous alirocumab 150 mg every 4 weeks (Q4W, n=54), alirocumab 150 mg every 2 weeks (Q2W, n=53), or placebo (n=56) over a 12-week double-blind treatment period followed by an open-label treatment period of 52 weeks.
During the open-label treatment period, patients received alirocumab 150 mg every 4 weeks with up-titration to 150 mg every 2 weeks at week 24 if participants did not meet LDL-C reduction goals at week 20. The primary efficacy end point was mean change in LDL-C from baseline to week 12; primary safety outcomes were assessed by analyzing adverse events.
At week 12, the least-square mean percent change in LDL-C was -43.8% ±2.2% for the alirocumab Q4W group, -70.1% for the alirocumab Q2W group, and -4.3% for the placebo group; in stratified analysis, the effect of alirocumab was similar for both statin presence and statin absence.
By week 12, 85.2% of the alirocumab Q4W group achieved their LDL-C goals compared with 96.2% of the alirocumab Q2W group and 14.3% of the placebo group. During the open-label treatment period, the mean change in LDL-C was -45.1% from baseline to week 20 with further reductions observed at week 36, which were maintained through the end of the study.
During the 12-week double-blind treatment period, at least 1 adverse event was reported by 51.9% of the alirocumab Q4W group, 47.2% of the alirocumab Q2W group, and 46.4% of the placebo group. Only 4 participants reported serious adverse events, including 1 in the alirocumab Q4W group, 2 in the alirocumab Q2W group, and 1 in the placebo group.
Infections and infestations (25.9% Q4W, 22.6% Q2W, 17.9% placebo) were the most common adverse events reported, followed by gastrointestinal disorders (13.0% Q4W, 9.4% Q2W, 12.5% placebo), nervous system disorders (5.6% Q4W, 7.5% Q2W, 10.7% placebo), and general complaints and administration-site reactions (3.7% Q4W, 11.3% Q2W, 5.4% placebo).
During the 52-week open-label treatment period, 69.0% of participants reported any occurrence of an adverse event; 12 patients (7.6%) reported a serious adverse event. Seven patients (4.4%) discontinued treatment due to an adverse event, but no deaths related to treatment were reported.
A limitation of the study included a more conservative dose of atorvastatin than used in regions outside of Japan, which prevents the generalizability of the study results to other populations.
The investigators indicated that alirocumab dosing of 150 mg every 4 weeks — in addition to lowest-strength statin or nonstatin lipid-lowering therapies — was efficacious in lowering LDL-C in Japanese patients with hypercholesterolemia, and was further well tolerated by the population and showed no new safety signals.
This study is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Teramoto T, Kiyosue A, Ishigaki Y, et al. Efficacy and safety of alirocumab 150 mg every 4 weeks in hypercholesterolemic patients on non-statin lipid-lowering therapy or lowest strength dose of statin: ODYSSEY NIPPON [published online November 30, 2018]. J Cardiol. doi:10.1016/j.jjcc.2018.10.004