Familial Chylomicronemia Syndrome Treatment Shows Positive Results in Phase 3 Trial
Results from the PALISADE study were published in The New England Journal of Medicine.
Positive results have been announced from a phase 3 trial evaluating the safety and efficacy of plozasiran for the treatment of adult patients with genetically confirmed or clinically diagnosed familial chylomicronemia syndrome (FCS), Arrowhead Pharmaceuticals announced in a release.1 Based on the data, the company said that it intends to file a new drug application with the FDA by the end of this year.
Familial Chylomicronemia Syndrome Treatment Shows Positive Results in Phase 3 Trial / catalin - stock.adobe.com
Data from the PALISADE (NCT05089084) study showed that plozasiran met its primary endpoint of percent change from baseline in fasting triglycerides at Month 10. The therapy also met all of its key secondary endpoints, including percent change from baseline in apolipoprotein C-III (APOC3), percent change from baseline in non-high density lipoprotein cholesterol (Non-HDL-C), and number of participants with positively adjudicated events of acute pancreatitis.
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Results from the PALISADE study were presented in a late-breaking oral presentation at the European Society of Cardiology Congress 2024 and were also published in The New England Journal of Medicine.2
“Plozasiran demonstrated very deep reductions in triglycerides in the PALISADE study and is the only investigational medicine to achieve a statistically significant reduction in the risk of developing acute pancreatitis in patients with genetically confirmed and clinically diagnosed FCS in a controlled study,” Gerald F. Watts, DSc, MD, PhD, professor of cardio-metabolic medicine at the University of Western Australia, said in a release.1 “These results are encouraging and offer hope to people living with FCS and their physicians who are in desperate need of new safe and effective treatment options.”
PALISADE was a randomized, placebo controlled phase 3 study evaluating the safety and efficacy of plozasiran. The study cohort included 75 adult patients with either genetically confirmed or clinically diagnosed persistent FCS. Patients in the study received either placebo or 25 mg or 50 mg of subcutaneous plozasiran every 3 months for 12 months. The median triglyceride level was 2044 mg/dL at baseline.
The study found that the median change from baseline in the fasting triglyceride level was −80% in the 25 mg plozasiran group and −78% in the 50 mg group, compared to -17% in the placebo group. APOC3 was significantly reduced at month 10 in the treatment groups, with -93% in the 25 mg plozasiran group and -96% in the 50 mg group. Additionally, patients receiving plozasiran achieved an 83% reduction in the risk of developing acute pancreatitis.
Plozasiran was also seen to have a favorable safety profile, with adverse events in the treatment groups being generally similar to those in the placebo group. However, both severe and serious adverse events were more common in the placebo group. The most common adverse events were abdominal pain, COVID-19, nasopharyngitis, headache, nausea, back pain, diarrhea, and upper respiratory tract infection.
“Based on the data generated to date, we view plozasiran as potentially best-in-class and supportive of development across the spectrum of triglyceride disorders,” Bruce Given, MD, chief medical scientist at Arrowhead, said in a release.1 “[W]e showed that in PALISADE a high proportion of patients receiving plozasiran achieved triglyceride levels below guideline-directed risk thresholds associated with the risk of acute pancreatitis, which is a critical treatment goal that physicians communicate to us frequently.”
FCS is a rare recessive metabolic disorder that is caused by mutations in the lipoprotein lipase and is associated with significant morbidity and distress. The condition affects around 3000 to 5000 patients globally, though it is likely underreported due to its vague symptoms.3 There are currently no approved treatments for the disorder in the US.
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