- •Volanesorsen is approved in Europe to treat familial chylomicronaemia syndrome.
- •Long-term triglyceride reduction (up to 51 months) is maintained with volanesorsen.
- •No new safety signals were associated with increased exposure to volanesorsen.
- •Volanesorsen is an effective treatment option for familial chylomicronaemia syndrome.
Background and aims
The VOL4002 study assessed the efficacy and safety of volanesorsen in 22 adults with genetically confirmed familial chylomicronaemia syndrome (FCS) treated in the UK Early Access to Medicines Scheme (EAMS), with (“prior exposure”) or without (“treatment naive”) previous treatment in the APPROACH and/or APPROACH-OLE volanesorsen phase 3 studies.
Data collection focused on triglyceride (TG) levels, platelet counts and pancreatitis events. Pancreatitis incidence during volanesorsen treatment was compared against the 5-year period preceding volanesorsen exposure. Volanesorsen 285 mg was self-administered subcutaneously once every 2 weeks.
Individual patient volanesorsen exposure ranged from 6 to 51 months (total cumulative exposure, 589 months). Among treatment-naive patients (n = 12), volanesorsen treatment resulted in an averaged median 52% reduction (−10.6 mmol/L) from baseline (26.4 mmol/L) in TG levels at 3 months, which were maintained through time points over 15 months of treatment (47%–55% reductions). Similarly, prior-exposure patients (n = 10) experienced a 51% reduction (−17.8 mmol/L) from pre-treatment baseline (28.0 mmol/L), with reductions of 10%–38% over 21 months of treatment. A comparison of pancreatitis event rates found a 74% reduction from the 5-year period before (one event/2.8 years) and during (one event/11.0 years) volanesorsen treatment. Platelet declines were consistent with observations in phase 3 clinical trials. No patient recorded a platelet count <50 × 109/L.
This longitudinal study supports the efficacy of volanesorsen in patients with FCS for lowering TG levels over treatment periods up to 51 months with no apparent safety signals related to increased duration of exposure.
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- Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia.Eur. Heart J. 2020; 41: 3936-3945https://doi.org/10.1093/eurheartj/ehaa689
- The burden of familial chylomicronemia syndrome: results from the global IN-FOCUS study.J Clin Lipidol. 2018; 12: 898-907.e2https://doi.org/10.1016/j.jacl.2018.04.009
- Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement.Lancet Diabetes Endocrinol. 2020; 8: 50-67https://doi.org/10.1016/S2213-8587(19)30264-5
- Clinical and biochemical features of different molecular etiologies of familial chylomicronemia.J Clin Lipidol. 2018; 12 (7.e4): 920https://doi.org/10.1016/j.jacl.2018.03.093
- Characterizing familial chylomicronemia syndrome: baseline data of the APPROACH study.J Clin Lipidol. 2018; 12 (43.e5): 1234https://doi.org/10.1016/j.jacl.2018.05.013
- Building a better understanding of the burden of disease in familial chylomicronemia syndrome.Expet Rev. Clin. Pharmacol. 2017; 10: 1-3https://doi.org/10.1080/17512433.2017.1251839
- Development of a novel PRO instrument for use in familial chylomicronemia syndrome.J Patient Rep Outcomes. 2021; 5: 72https://doi.org/10.1186/s41687-021-00347-5
- Volanesorsen in the treatment of familial chylomicronemia syndrome or hypertriglyceridaemia: design, development and place in therapy.Drug Des. Dev. Ther. 2020; 14: 2623-2636https://doi.org/10.2147/DDDT.S224771
- Targeting APOC3 in the familial chylomicronemia syndrome.N. Engl. J. Med. 2014; 371: 2200-2206https://doi.org/10.1056/NEJMoa1400284
- Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia.N. Engl. J. Med. 2015; 373: 438-447https://doi.org/10.1056/NEJMoa1400283
- First global approval.Drugs. 2019; 79: 1349-1354https://doi.org/10.1007/s40265-019-01168-z
- Volanesorsen and triglyceride levels in familial chylomicronemia syndrome.N. Engl. J. Med. 2019; 381: 531-542https://doi.org/10.1056/NEJMoa1715944
- Natural history (up to 15 years) of platelet count in 84 patients with familial hyperchylomicronemia due to lipoprotein lipase deficiency [abstract].J Clin Lipidol. 2017; 11: 797-798
Published online: May 15, 2023
Accepted: May 9, 2023
Received in revised form: May 5, 2023
Received: October 24, 2022Handling Editor: Dr. A. von Eckardstein
© 2023 Elsevier B.V. All rights reserved.