Trial results for the Phase 3 study (NCT04659863) investigating inclisiran in adolescents with homozygous familial hypercholesterolemia (HoFH) were posted on ClinicalTrials.gov on 2025-05-31. The study showed that participants receiving inclisiran achieved a mean LDL-C reduction of -21.6% from baseline to Day 330, compared to a mean increase of 11.7% for those on placebo. The mean net difference in LDL-C change was -33.25%.
Background
The study, titled "Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia," aimed to evaluate the safety, tolerability, and efficacy of inclisiran in adolescents with HoFH and elevated low-density lipoprotein cholesterol (LDL-C).
Trial design
The study (NCT04659863) was a pivotal Phase 3, randomized, placebo-controlled trial that enrolled 13 participants. The study investigated inclisiran in adolescents diagnosed with Homozygous Familial Hypercholesterolemia. Participants were assigned to receive either inclisiran or placebo. The study's primary focus included evaluating the percentage change in LDL-C from baseline.
Key results
The trial results demonstrated differences in LDL-C reduction between the inclisiran and placebo groups.
- For "Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)":
- Participants receiving inclisiran showed a mean change of -21.6% (Standard Deviation: 13.36).
- Participants receiving placebo showed a mean change of 11.7% (Standard Deviation: 30.52).
- For "Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1)":
- Participants receiving inclisiran showed a mean change of -21.0% (Standard Deviation: 15.11).
- Participants receiving placebo showed a mean change of 13.0% (Standard Deviation: 41.88).
- For "Percent Change in LDL-C From Baseline up to Day 720" (first measurement):
- Participants receiving inclisiran showed a mean change of -26.1% (Standard Deviation: 13.53).
- Participants receiving placebo showed a mean change of 6.8% (Standard Deviation: 16.83).
- For "Percent Change in LDL-C From Baseline up to Day 720" (second measurement):
- Participants receiving inclisiran showed a mean change of -24.1% (Standard Deviation: 14.65).
- Participants receiving placebo showed a mean change of 17.0% (Standard Deviation: 41.22).
- For "Percent Change in LDL-C From Baseline up to Day 720" (third measurement):
- Participants receiving inclisiran showed a mean change of -17.3% (Standard Deviation: 21.64).
- Participants receiving placebo showed a mean change of 10.2% (Standard Deviation: 54.00).
An analysis of the mean difference (net) in LDL-C change showed a value of -33.25% (95.0% CI: -59.17 to -7.34).
What this means
The results from this Phase 3 trial suggest that inclisiran can reduce LDL-C levels in adolescents with homozygous familial hypercholesterolemia. The observed reductions in LDL-C compared to placebo indicate its potential as a therapeutic option for managing this severe genetic condition, which is characterized by very high LDL-C levels from birth and premature cardiovascular disease.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04659863, titled "Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia," were posted on 2025-05-31 on clinicaltrials.gov.