Olezarsen reduces triglycerides, pancreatitis events in familial chylomicronemia syndrome
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Key takeaways:
- At 6 months, triglyceride levels were significantly reduced in patients with FCS who received 80 mg of olezarsen every 4 weeks (–43.5%).
- This effect was not observed in those receiving 50 mg (–22.4%).
Monthly olezarsen 80 mg significantly lowered triglyceride levels and also reduced incidence of acute pancreatitis vs. placebo in patients with familial chylomicronemia syndrome, according to a study in The New England Journal of Medicine.
The investigational drug, a GalNAc3-conjugated antisense oligonucleotide, was granted orphan drug and breakthrough therapy designations by the FDA in February for treatment of familial chylomicronemia syndrome (FCS), according to an Ionis Pharmaceuticals press release.
“As a physician who has seen firsthand the struggles of people living with FCS and its serious complications, there is significant need for an effective therapy to lower triglycerides and reduce acute pancreatitis events,” Erik S.G. Stroes, MD, PhD, study author and professor of medicine at Amsterdam University Medical Center, said in the release. “Olezarsen represents a potentially life-changing new medicine for these patients who experience debilitating chronic symptoms, including abdominal pain and cognitive symptoms, as well as hospitalizations associated with potentially fatal acute pancreatitis events.”
In a phase 3, double-blind, placebo-controlled trial, 66 adult patients with genetically identified FCS received subcutaneous olezarsen 80 mg (n = 22; mean age, 47.7 years) or 50 mg (n = 21; mean age, 43.2 years) or placebo (n = 23; mean age, 44 years) every 4 weeks for 53 weeks. The primary endpoint was percent change in fasting triglyceride levels from baseline to 6 months between groups. Secondary endpoints included mean percent change from baseline in apolipoprotein C-III level, as well as the incidence of acute pancreatitis.
According to results, at baseline the mean triglyceride level was 2,630 mg per deciliter, and 71% of patients had a history of acute pancreatitis within the previous 10 years.
Triglyceride levels were significantly reduced at 6 months with 80 mg olezarsen (–43.5%; 95% CI, –69.1 to –17.9); however, researchers did not observe this effect in the 50 mg group (–22.4%; 95% CI, –47.2 to 2.5). The difference in mean percent change in apolipoprotein C-III level from baseline to 6 months was –73.7% (95% CI, –94.6 to –52.8) between the 80 mg and placebo groups and –65.5% (95% CI, –82.6 to –48.3) between the 50 mg and placebo groups.
Stroes and colleagues reported 11 episodes of acute pancreatitis in the placebo group by week 53 and one episode in each olezarsen group. Moderate adverse events related to the trial drug occurred among four patients in the 80 mg olezarsen group.
“Among patients with familial chylomicronemia syndrome, olezarsen, administered at a dose of 80 mg every 4 weeks, reduced triglyceride levels significantly more than placebo; the lower dose of 50 mg did not,” Stroes and colleagues wrote. “These findings, together with the safety data, support further clinical research of olezarsen as a pharmacologic treatment for familial chylomicronemia syndrome.”
Reference:
- Ionis presents positive results from phase 3 Balance study of olezarsen for familial chylomicronemia syndrome. https://ir.ionispharma.com/news-releases/news-release-details/ionis-presents-positive-results-phase-3-balance-study-olezarsen. Published April 7, 2024. Accessed April 24, 2024.
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