3 The technology

3.1 Inotersen (Tegsedi, Akcea Therapeutics) is a novel, first-in-class 2'‑O‑2‑methoxyethyl phosphorothioate antisense oligonucleotide that inhibits production of transthyretin (TTR) in adults with hereditary transthyretin (hATTR) amyloidosis. Inotersen has a marketing authorisation for 'the treatment of stage 1 or stage 2 polyneuropathy in adults with hATTR amyloidosis'.

3.2 The most frequent adverse reaction listed in the summary of product characteristics is injection site reactions (50.9%). Other commonly reported adverse reactions are nausea (31.3%), anaemia (27.7%), headache (23.2%), pyrexia (19.6%), peripheral oedema (18.8%), chills (17.9%), vomiting (15.2%), thrombocytopenia (13.4%) and decreased platelet count (10.7%). In the main clinical trial for inotersen (the NEURO‑TTR study) there was 1 death, which was considered to be related to inotersen. The main safety concerns with inotersen treatment are glomerulonephritis and thrombocytopenia, therefore enhanced monitoring (platelet count, urine protein to creatinine ratio and estimated glomerular filtration rate [eGFR]) has been implemented. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.3 Inotersen is self-administered once weekly by subcutaneous injection. The price of inotersen per weekly dose (284 mg) is £5,925 (excluding VAT; company submission). The company has a commercial arrangement. This makes inotersen 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)