Long-acting LDL-lowering drug shows sustained benefit with only 1 or 2 doses

Takeaway

• A couple of doses of cholesterol-reducing inclisiran kept low-density lipoprotein cholesterol (LDL-C) levels reduced for a year.
• 2 doses offered steeper lasting reductions than 1.
• These 1-year findings are from a prespecified analysis of the ORION-1 trial of this small-interfering RNA drug.

Why this matters

• Editorial predicts that "the world of statins and vaccines are about to collide" with attendant concerns and "fear-mongering" from some quarters.

Key results

• With 1 dose, 48.3%-65.0% of participants did not return to within 20% of their change in baseline LDL-C at 1 year.
• With 2 doses, this range was 55.9%-83.1%.
• Time-averaged decreases over a year for the single-dose group were 29.5%-38.7%.
• They were 29.9%-46.4% for the 2-dose group, which also had the most responders and steepest reductions at 1 year.
• A second 300-mg dose (given at day 90) yielded an additional decrease over the single dose of about 10% (P=.002).
• The 2 groups had similar incidence of adverse events, with 2 deaths not attributed to drug.

Study design

• ORION-1 was a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial.
• Doses: 1 dose at 200, 300, or 500 mg on day 1, or 2 doses of 100, 200, or 300 mg on days 1 and 90.
• Funding: The Medicines Company.

Limitations

• Included only patients whose LDL-C had not increased to within 20% of change from baseline.