Long-term effects of volanesorsen on triglycerides and pancreatitis in patients with familial chylomicronaemia syndrome (FCS) in the UK Early Access to Medicines Scheme (EAMS)
- PMID: 37253281
- DOI: 10.1016/j.atherosclerosis.2023.05.008
Long-term effects of volanesorsen on triglycerides and pancreatitis in patients with familial chylomicronaemia syndrome (FCS) in the UK Early Access to Medicines Scheme (EAMS)
Abstract
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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: Familial chylomicronaemia syndrome; Hypertriglyceridemia; Lipoprotein lipase; Pancreatitis; Volanesorsen.
Copyright © 2023 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:AJ has no conflicts of interest to declare.KP has no conflicts of interest to declare.ASW is a site investigator for clinical trials for Akcea, Amgen, Regeneron, and Sanofi.RR has no conflicts of interest to declare.MM has no conflicts of interest to declare. CD has no conflicts of interest to declare.AOF has no conflicts of interest to declare.HS has received research and education grants and honoraria from Akcea Therapeutics.FJ has no conflicts of interest to declare.IM has no conflicts of interest to declare.PD has received speaker fees and honoraria from Akcea Therapeutics for attendance at Advisory boards.PH has no conflicts of interest to declare.RJ was an employee of Akcea Therapeutics at the time the study was undertaken.
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