Volanesorsen reduces acute pancreatitis in patients with severe hypertriglyceridaemia, according to results of a fixed-effects meta-analysis of individual patient data from three randomised, controlled trials that included patients with a TG level of >500 mg/dL (5.6 mmol/L).1-3
Of the 207 patients in the analysis, reported in the New England Journal of Medicine, 121 received volanesorsen (300 mg per week subcutaneously) and 86 received placebo. Mean treatment duration was 8.1 months, with a further follow up of three months. Acute pancreatitis was a secondary or exploratory endpoint in the three trials.
Before randomisation, acute pancreatitis had occurred in 40% of the patients in the volanesorsen group and in 51% of those in the placebo group, and the mean fasting TG was 1,543+1,060 mg/dL and 1,714+1,273 mg/dL, respectively.
During randomised treatment, acute pancreatitis occurred in two patients (2%) in the volanesorsen group and nine patients (10%) in the placebo group (odds ratio, 0.18; 95% confidence interval, 0.04 to 0.82).
Pancreatitis had occurred before randomisation in 10/11 patients who had acute pancreatitis during randomised treatment. No cases of acute pancreatitis occurred in the volanesorsen group more than four months after the start of trial treatment, but cases of acute pancreatitis occurred in the placebo group throughout randomised treatment.
During the trial, 102/121 (84%) patients taking volanesorsen achieved a TG <500 mg/dL compared with 30/86 (35%) in the placebo group.
The study researchers conclude that if the association between volanesorsen and a reduced incidence of acute pancreatitis is confirmed, inhibition of apoC3 expression may be a therapeutic strategy for patients with complications from severe hypertriglyceridaemia.
References
- Witztum JL, Gaudet D, Freedman SD, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med 2019; 381: 531-42.
- Gouni-Berthold I, Alexander VJ, Yang Q, et al. Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 2021; 9: 264-75.
- Oral EA, Garg A, Tami J, et al. Assessment of efficacy and safety of volanesorsen for treatment of metabolic complications in patients with familial partial lipodystrophy: results of the BROADEN study: volanesorsen in FPLD; the BROADEN study. J Clin Lipidol 2022; 16: 833-49.
- Alexander VJ, Karwatowska-Prokopczuk E, Prohaska TA et al. Volanesorsen to prevent acute pancreatitis in hypertriglyceridemia. N Engl J Med. 2024 Feb 1;390(5):476-477.
