The Phase 3 study evaluating Plozasiran (ARO-APOC3) in adults with Familial Chylomicronemia Syndrome (FCS) reached primary completion on 2024-04-29. Data from the trial showed that the 25 mg dose of Plozasiran led to a median 80.1% reduction in fasting triglycerides at Month 10 compared to a 17.1% reduction with placebo.
Background
Plozasiran (also known as ARO-APOC3) is an investigational drug studied for the treatment of Familial Chylomicronemia Syndrome (FCS). FCS is a rare genetic disorder characterized by severely elevated triglyceride levels, which can lead to complications such as recurrent pancreatitis.
Trial design
The Phase 3 study (NCT05089084) enrolled 75 adult participants with Familial Chylomicronemia Syndrome (FCS). The trial aimed to evaluate the efficacy and safety of Plozasiran (ARO-APOC3) compared to placebo. Participants were randomized to receive either Plozasiran at doses of 25 mg or 50 mg, or matching placebo, administered subcutaneously over a randomized period. Following this, participants could continue into a 2-year open-label extension period where all would receive Plozasiran.
Key results
The trial reported significant reductions in fasting triglycerides and Apolipoprotein C-III (APOC3) levels:
- Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG):
- Plozasiran 25 mg group: median reduction of -80.1 percentage change.
- Plozasiran 50 mg group: median reduction of -77.6 percentage change.
- Placebo group: median reduction of -17.1 percentage change.
- Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged):
- Plozasiran 25 mg group: median reduction of -77.7 percentage change.
- Plozasiran 50 mg group: median reduction of -71.0 percentage change.
- Placebo group: median reduction of -2.6 percentage change.
- Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10:
- Plozasiran 25 mg group: median reduction of -92.95 percentage change.
- Plozasiran 50 mg group: median reduction of -96.20 percentage change.
- Placebo group: median reduction of -1.25 percentage change.
- Percent Change From Baseline in Fasting APOC3 at Month 12:
- Plozasiran 25 mg group: median reduction of -89.30 percentage change.
- Plozasiran 50 mg group: median reduction of -87.73 percentage change.
- Placebo group: median increase of 7.69 percentage change.
Statistical analyses confirmed these differences:
- A Wilcoxon rank-sum test showed a median difference in final values of -58.7 (95.0% CI: -89.6, -27.9) with a p-value of 0.0001.
- Another Wilcoxon rank-sum test showed a median difference in final values of -52.5 (95.0% CI: -83.1, -21.9) with a p-value of 0.0002.
- A further Wilcoxon rank-sum test showed a median difference in final values of -59.6 (95.0% CI: -91.6, -27.5) with a p-value of 0.0001.
What this means
The completion of this Phase 3 trial for Plozasiran in Familial Chylomicronemia Syndrome marks a significant step in its development. The observed substantial reductions in fasting triglycerides and Apolipoprotein C-III levels across both active treatment arms, compared to placebo, indicate a strong potential for Plozasiran to address the high triglyceride burden characteristic of FCS. These positive results suggest that Plozasiran could offer a new therapeutic option for patients with this rare genetic disorder, potentially reducing the risk of associated complications such as pancreatitis. Further regulatory review will determine its availability.
Source
The information regarding the primary completion and results of this trial was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT05089084, titled "Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS)", were posted on 2024-04-29 on clinicaltrials.gov.