Title: Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol

Kausik, KR, MD, et al.


What You Need to Know:

For patients with elevated low-density lipoprotein cholesterol (LDL-C) at high risk for cardiovascular (CV) disease, inclisiran, a chemically synthesized small interfering RNA that targets PCSK9 messenger RNA, was found to reduce PCSK9 and LDL-C.

Trial Design:

  • Phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending trial
  • Patients randomly assigned to single subcutaneous injection of placebo or inclisiran 200mg, 300mg, or 500mg, or two doses (Days 1 and 90) of placebo or 100mg, 200mg, or 300mg inclisiran
  • Primary endpoint: change from baseline in LDL-C at 180 days

Key Outcomes:

  • 501 patients were included
  • Dose-dependent reductions in PCSK9 and LDL-C were seen in patients receiving inclisiran
  • Least-squares mean reductions in LDL-C: single dose: 27.9–41.9%; two doses: 35.5–52.6% (P<0.001 for all comparisons vs. placebo)
  • Greatest LDL-C reduction with two-dose 300mg regimen: 48% of patients had LDL-C <50mg/dL at Day 180
  • For all inclisiran regimens: PCSK9 and LDL-C remained significantly lower than at baseline at Day 240
  • Serious adverse events: 11% for inclisiran vs. 8% for placebo
  • Injection-site reactions occurred in 5% of patients receiving inclisiran