Inotersen for treating hereditary transthyretin-related amyloidosis (NICE Highly Specialised Technologies Assessment)

To critically appraise the company submitted evidence to NICE’s Highly Specialised Technologies (HST) programme, regarding the clinical and cost-effectiveness of Inotersen (Tegsedi®, Ionis USA Ltd, London, UK) for treating Hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN)

As part of the NICE HST process, the Aberdeen evidence review group (ERG) were commissioned to critically review the company’s submission related to the clinical and cost-effectiveness of Inotersen for treating Hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN).

The clinical-effectiveness evidence focussed on a phase 3, double-blind, placebo-controlled, multi-centre RCT (NEURO-TTR) followed by an open label extension study in the same population. The study randomised 173 participants (2:1 to inotersen 300mg or placebo). The co-primary outcomes were change from baseline to week 66 in A) Modified neuropathy impairment score +7 composite score (mNIS+7) and B) Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QoL-DN) questionnaire total score.

The economic evidence was based on a Markov cohort state transition model, with a lifetime horizon, from an NHS and PSS perspective. The model described the progression of disease according to Coutinho disease stages using transition probabilities based on the NEURO-TTR study.

Outcome and Translation

Based on consideration of evidence submitted by Tegsedi® and a review of the company submitted evidence by the evidence review group, NICE recommended Inotersen, within its marketing authorisation, as an option for treating stage 1 and stage 2 polyneuropathy in adults with hereditary transthyretin amyloidosis under the terms of a commercial arrangement.

Details of the appraisal and the full guidance are available on the NICE website: Inotersen for treating hereditary transthyretin amyloidosis. Highly specialised technologies guidance [HST9].

HERU researchers involved in this project: Dwayne Boyers and Graham Scotland 

External collaborators: C. Ramsay, M. Brazzelli, E. Cummins and M. Campbell (Health Services Research Unit (HSRU), University of Aberdeen)


Boyers, D., Fielding, S., Cruickshank, M., Imamura, M., Fraser, C., Tighe, J. and Scotland, G. (2018) Inotersen for treating hereditary transthyretin-related amyloidosis, (NICE Highly Specialised Technologies programme), Aberdeen Health Technology Assessment Group.