Highlights
- •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.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: May 15, 2023
Accepted:
May 9,
2023
Received in revised form:
May 5,
2023
Received:
October 24,
2022
Handling Editor: Dr. A. von EckardsteinIdentification
Copyright
© 2023 Elsevier B.V. All rights reserved.
