Trial results for inclisiran as monotherapy in patients with primary hypercholesterolemia were posted on ClinicalTrials.gov on 2025-08-13. The study demonstrated that inclisiran reduced Low-Density Lipoprotein Cholesterol (LDL-C) by an average of -46.54% from baseline to Day 150, compared to -11.17% for ezetimibe and 1.37% for placebo.
Background
The study investigated inclisiran in participants with primary hypercholesterolemia who were not receiving any lipid-lowering therapy (LLT). These participants had a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk of less than 7.5%.
Trial design
The study (NCT05763875) was a Phase 3 clinical trial that enrolled 350 participants. It investigated the efficacy and safety of inclisiran as monotherapy in patients with primary hypercholesterolemia who were not receiving lipid-lowering therapy and had a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk of less than 7.5%. The study compared inclisiran to ezetimibe and placebo. The primary objective was to determine if inclisiran effectively reduces Low-Density Lipoprotein Cholesterol (LDL-C) as measured by percentage change from baseline to Day 150.
Key results
The trial evaluated the percentage and absolute change in Low-Density Lipoprotein Cholesterol (LDL-C) from baseline to Day 150 across the treatment groups.
- For "Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150":
- Inclisiran showed least squares mean changes of -46.54% and -49.37%.
- Ezetimibe showed least squares mean changes of -11.17% and -11.92%.
- Placebo showed least squares mean changes of 1.37% and -1.53%.
- For "Absolute Change in LDL-C From Baseline to Day 150":
- Inclisiran showed least squares mean changes of -64.86 mg/dL and -68.57 mg/dL.
- Ezetimibe showed least squares mean changes of -17.55 mg/dL and -18.52 mg/dL.
- Placebo showed least squares mean changes of -1.29 mg/dL and -1.07 mg/dL.
Key analyses comparing the treatment groups included:
- For percentage change in LDL-C (Treatment Policy Estimand): The least squares mean difference for inclisiran versus ezetimibe was -35.37 (95.0% CI: -40.88 to -29.86), with a p-value of 0.0001.
- For percentage change in LDL-C (Treatment Policy Estimand): The least squares mean difference for inclisiran versus placebo was -47.91 (95.0% CI: -53.62 to -42.2), with a p-value of 0.0001.
- For percentage change in LDL-C (Monotherapy Estimand): The least squares mean difference for inclisiran versus ezetimibe was -37.44 (95.0% CI: -42.63 to -32.26), with a p-value of 0.0001.
- For percentage change in LDL-C (Monotherapy Estimand): The least squares mean difference for inclisiran versus placebo was -50.9 (95.0% CI: -56.51 to -45.28), with a p-value of 0.0001.
- For absolute change in LDL-C (Treatment Policy Estimand): The least squares mean difference for inclisiran versus ezetimibe was -47.37 (95.0% CI: -53.91 to -40.72), with a p-value of 0.0001.
- For absolute change in LDL-C (Treatment Policy Estimand): The least squares mean difference for inclisiran versus placebo was -63.57 (95.0% CI: -70.28 to -56.87), with a p-value of 0.0001.
What this means
The results from this Phase 3 trial indicate that inclisiran monotherapy significantly reduced LDL-C levels in patients with primary hypercholesterolemia. The substantial percentage and absolute reductions in LDL-C, along with the statistically significant differences observed when compared to both ezetimibe and placebo, suggest that inclisiran could be an effective treatment option for individuals with this condition who are not currently receiving other lipid-lowering therapies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05763875, titled "Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy," were posted on 2025-08-13 on clinicaltrials.gov.