3 The technology

3.1 Volanesorsen (Waylivra, Akcea) is an antisense oligonucleotide inhibitor of apolipoprotein C‑III (apoC‑III) production. ApoC‑III inhibits the metabolism of triglycerides via the actions of both the lipoprotein lipase and lipoprotein lipase‑independent pathways. It selectively binds to apoC‑III mRNA to prevent the production of the apoC‑III protein, so increasing metabolism of triglycerides. Volanesorsen has a marketing authorisation 'as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome (FCS) and at high risk for pancreatitis, in whom response to diet and triglyceride-lowering therapy has been inadequate'. Volanesorsen is administered by subcutaneous injection. The recommended starting dosage, as described in the summary of product characteristics, is 285 mg once weekly for 3 months, followed by down titration to a maintenance dosing schedule of once every 2 weeks. If there has not been a greater than 25% reduction in triglyceride levels, or if these remain above 22.6 mmol per litre at 3 months, treatment should be stopped. If response is inadequate (in terms of serum triglyceride reduction) after 6 months of treatment, an increase in dosing frequency to 285 mg once weekly should be considered. Dosing may also change at 9 months and later depending on response to treatment and platelet levels.

3.2 The adverse reactions listed as very common (that is, occurring in 1 in 10 people or more) in the summary of product characteristics for volanesorsen include thrombocytopenia and injection site reactions. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.3 Before starting treatment with volanesorsen, platelet count should be measured. If it is below 140×109 per litre, another measurement should be taken about a week later to reassess. If platelet count remains below 140×109 per litre at a second measurement, treatment should not be started. Because of concerns about thrombocytopenia, an enhanced monitoring scheme has been implemented during clinical trials and in clinical practice. For full details of monitoring schedules, see the summary of product characteristics.

3.4 The price of volanesorsen for a single-use syringe (285 mg) is £11,394 (excluding VAT; company's evidence submission). The company has a commercial arrangement. This makes volanesorsen available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know details of the discount.

  • National Institute for Health and Care Excellence (NICE)