Results from a Phase 3 clinical trial evaluating Olezarsen in patients with Familial Chylomicronemia Syndrome (FCS) were posted on 2025-03-06. The trial demonstrated that Olezarsen 80 mg significantly reduced fasting triglycerides by 31.99% at Month 6 and 38.50% at Month 12 compared to baseline, with statistically significant differences versus placebo.
Background
Familial Chylomicronemia Syndrome (FCS) is a rare genetic disorder characterized by severely elevated triglyceride levels due to impaired breakdown of chylomicrons. Patients with FCS are at high risk for recurrent episodes of acute pancreatitis, which can be life-threatening, and often experience chronic abdominal pain, fatigue, and other debilitating symptoms. Effective management strategies are crucial for reducing triglyceride levels and mitigating associated risks.
Trial design
The completed Phase 3 study (NCT04568434) enrolled 66 participants with Familial Chylomicronemia Syndrome. The trial's purpose was to evaluate the efficacy of Olezarsen compared to placebo on the percent change in fasting triglycerides from baseline. Participants were randomized to receive either Olezarsen at doses of 50 mg or 80 mg, or placebo.
Key results
The trial assessed the percent change from baseline in fasting triglycerides (TG) and apolipoprotein C-III (apoC-III) at various time points:
- Percent Change From Baseline in Fasting TG at Month 6:
- Placebo: 11.52% increase
- Olezarsen 50 mg: -10.85% decrease
- Olezarsen 80 mg: -31.99% decrease
- Percent Change From Baseline in Fasting TG at Month 12:
- Placebo: 20.89% increase
- Olezarsen 50 mg: -22.92% decrease
- Olezarsen 80 mg: -38.50% decrease
Key analyses for the percent change from baseline in fasting TG demonstrated:
- At Month 6, Olezarsen 80 mg showed an LS mean difference of -43.5 (95% CI: -69.085, -17.921) versus placebo, with a p-value of 0.0009. The 50 mg dose had an LS mean difference of -22.37 (95% CI: -47.2, 2.463) with a p-value of 0.0775.
- At Month 12, Olezarsen 80 mg showed an LS mean difference of -59.39 (95% CI: -90.663, -28.119) versus placebo, with a p-value of 0.0002. The 50 mg dose had an LS mean difference of -43.81 (95% CI: -73.928, -13.692) with a p-value of 0.0044.
Additionally, significant reductions in fasting apolipoprotein C-III (apoC-III) were observed:
- Percent Change From Baseline in Fasting apoC-III at Month 6:
- Placebo: 7.57% increase
- Olezarsen 50 mg: -57.91% decrease
- Olezarsen 80 mg: -66.13% decrease
- Percent Change From Baseline in Fasting apoC-III at Month 12:
- Placebo: 17.08% increase
- Olezarsen 50 mg: -59.98% decrease
- Olezarsen 80 mg: -64.20% decrease
Key analyses for the percent change from baseline in fasting apoC-III at Month 6 demonstrated:
- Olezarsen 50 mg showed an LS mean difference of -65.48 (95% CI: -82.634, -48.32) versus placebo, with a p-value of 0.0001.
- Olezarsen 80 mg showed an LS mean difference of -73.69 (95% CI: -94.553, -52.837) versus placebo, with a p-value of 0.0001.
What this means
The results indicate that Olezarsen, particularly at the 80 mg dose, effectively reduced fasting triglyceride levels and apolipoprotein C-III in patients with Familial Chylomicronemia Syndrome. The statistically significant reductions observed at both 6 and 12 months suggest a sustained therapeutic effect. These findings are important for FCS patients, who currently have limited treatment options to manage their severely elevated triglycerides and reduce the risk of associated complications like pancreatitis.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04568434, titled "A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)," were posted on 2025-03-06 on clinicaltrials.gov.