Data Shows Volanesorsen to Provide Significant Reduction of Triglycerides in FCS

At the National Lipid Association (NLA) Scientific Sessions in Las Vegas, NV this morning, Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals, presented a poster with data from 2 different studies, each of which exhibited a significant reduction of triglycerides in patients with familial chylomicronemia syndrome (FCS) when administered volanesorsen.

In a pair of Phase 3 trials — APPROACH and COMPASS – treatment with the drug exhibited the ability to reduce triglycerides by 77% and by 71%, respectively.

FCS is a rare metabolic condition characterized by severe chylomicronemia, serum triglycerides (TG) that are 10 to100-fold above normal levels and consequent risk of recurrent and acute, potentially fatal, pancreatitis. It is caused by a deficiency in the production or functionality of lipoprotein lipase (LPL), the enzyme responsible for the break down of plasma TGs. Individuals with FCS commonly present with an array of symptoms because of these severely high TG levels, including physical, emotional, and cognitive symptoms which contribute to heightened disease burden and weakened quality of life (QoL).

At present, the only available option for patients who are looking to manage these symptoms is to follow an exceptionally restrictive, very low-fat diet (≤20 g daily), limit simple carbohydrates and abstain from alcohol, and even with this strict adherence, TGs have been shown to remain high, resulting in patients remaining at risk of acute pancreatitis.

The poster, “Treatment with Volanesorsen (VLN) Reduced Triglycerides and Pancreatitis in Patients with Familial Chylomicronemia Syndrome (FCS) and Severe Hypertriglyceridemia (sHTG) vs Placebo: Results of the APPROACH and COMPASS Studies,” displayed results from both the APPROACH trial, a randomized, double-blind, placebo-controlled, Phase 3 study of volanesorsen administered subcutaneously in patients with FCS (genetically confirmed or documented LPL activity of ≤20%); and the COMPASS trial, a randomized, double-blind, placebo-controlled, Phase 3 study of volanesorsen administered subcutaneously in patients with severe HTG (sHTG).

The Phase 3 APPROACH study, a randomized, double-blind, placebo-controlled, 52-week trial, enrolled 66 patients with FCS, and administered volanesorsen to half of all participants (n=33) and placebo to those remaining (n=33). At the study’s initiation, patients had an average triglyceride level of 2,209 mg/dL; after only 3 months of treatment, a reduction in triglyceride levels was achieved, as the volanesorsen-treated group exhibited a 77% reduction versus the placebo-treated group who reported an 18% increase in triglyceride level (P < .0001).

The COMPASS study was a 6-month randomized, placebo-controlled study in 113 patients with high triglycerides (>500 mg/dL). Its primary endpoint was also achieved, demonstrating a 71% reduction in triglycerides after 3 months of treatment with volanesorsen.

Incidence of pancreatitis was meaningfully reduced in patients treated with volanesorsen in the combined studies, and treatment with volanesorsen had a mostly well-tolerated safety profile.

The most commonly reported adverse events (AE) were mild local injection site reactions. platelet reductions did occur in both studies, but were manageable by dose pause, dose reduction and treatment with corticosteroids and intravenous immunoglobulin (IVIG).

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References:

Gelrud A, et al. Treatment with Volanesorsen (VLN) Reduced Triglycerides and Pancreatitis in Patients with Familial Chylomicronemia Syndrome (FCS) and Severe Hypertriglyceridemia (sHTG) vs Placebo: Results of the APPROACH and COMPASS Studies. Presented at: 2018 National Lipid Association (NLA) Scientific Sessions; April 26-29, 2018; Las Vegas, Nevada.