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Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome.
- Source :
-
The New England journal of medicine [N Engl J Med] 2024 May 16; Vol. 390 (19), pp. 1781-1792. Date of Electronic Publication: 2024 Apr 07. - Publication Year :
- 2024
-
Abstract
- Background: Familial chylomicronemia syndrome is a genetic disorder associated with severe hypertriglyceridemia and severe acute pancreatitis. Olezarsen reduces the plasma triglyceride level by reducing hepatic synthesis of apolipoprotein C-III.<br />Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with genetically identified familial chylomicronemia syndrome to receive olezarsen at a dose of 80 mg or 50 mg or placebo subcutaneously every 4 weeks for 49 weeks. There were two primary end points: the difference between the 80-mg olezarsen group and the placebo group in the percent change in the fasting triglyceride level from baseline to 6 months, and (to be assessed if the first was significant) the difference between the 50-mg olezarsen group and the placebo group. Secondary end points included the mean percent change from baseline in the apolipoprotein C-III level and an independently adjudicated episode of acute pancreatitis.<br />Results: A total of 66 patients underwent randomization; 22 were assigned to the 80-mg olezarsen group, 21 to the 50-mg olezarsen group, and 23 to the placebo group. At baseline, the mean (±SD) triglyceride level among the patients was 2630±1315 mg per deciliter, and 71% had a history of acute pancreatitis within the previous 10 years. Triglyceride levels at 6 months were significantly reduced with the 80-mg dose of olezarsen as compared with placebo (-43.5 percentage points; 95% confidence interval [CI], -69.1 to -17.9; P<0.001) but not with the 50-mg dose (-22.4 percentage points; 95% CI, -47.2 to 2.5; Pā=ā0.08). The difference in the mean percent change in the apolipoprotein C-III level from baseline to 6 months in the 80-mg group as compared with the placebo group was -73.7 percentage points (95% CI, -94.6 to -52.8) and between the 50-mg group as compared with the placebo group was -65.5 percentage points (95% CI, -82.6 to -48.3). By 53 weeks, 11 episodes of acute pancreatitis had occurred in the placebo group, and 1 episode had occurred in each olezarsen group (rate ratio [pooled olezarsen groups vs. placebo], 0.12; 95% CI, 0.02 to 0.66). Adverse events of moderate severity that were considered by a trial investigator at the site to be related to the trial drug or placebo occurred in 4 patients in the 80-mg olezarsen group.<br />Conclusions: In patients with familial chylomicronemia syndrome, olezarsen may represent a new therapy to reduce plasma triglyceride levels. (Funded by Ionis Pharmaceuticals; Balance ClinicalTrials.gov number, NCT04568434.).<br /> (Copyright © 2024 Massachusetts Medical Society.)
- Subjects :
- Humans
Male
Female
Double-Blind Method
Middle Aged
Adult
Acute Disease
Oligonucleotides therapeutic use
Oligonucleotides adverse effects
Aged
Hypertriglyceridemia drug therapy
Hypertriglyceridemia blood
Young Adult
Pancreatitis drug therapy
Apolipoprotein C-III blood
Triglycerides blood
Hyperlipoproteinemia Type I drug therapy
Hyperlipoproteinemia Type I blood
Hyperlipoproteinemia Type I complications
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 390
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38587247
- Full Text :
- https://doi.org/10.1056/NEJMoa2400201