Inotersen: First Global Approval
Ionis Pharmaceuticals and Akcea Therapeutics have developed inotersen (Tegsedi™), an antisense oligonucleotide inhibitor of mutant and wild-type human transthyretin (TTR), for the treatment of hereditary transthyretin amyloidosis (hATTR). Mutation of the TTR gene results in accumulation of TTR protein fragments as amyloid deposits throughout the organs in patients with hATTR, including the peripheral nervous system and the heart. Treatment with inotersen, which selectively binds to TTR mRNA, prevents the synthesis of TTR protein in the liver, thus reducing further amyloid deposition throughout the body. Subcutaneous administration of inotersen significantly reduced neurological progression and improved health-related quality of life in patients with hATTR and polyneuropathy in a phase III trial. Based on these results, inotersen was recently approved in the EU for the treatment of stage 1 or 2 polyneuropathy in adult patients with hATTR and is under evaluation in the USA and Canada for a similar indication. This article summarizes the milestones in the development of inotersen leading to this first approval.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflict of interest
During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Susan J. Keam is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.
- 1.Akcea Therapeutics. Akcea and Ionis receive positive EU CHMP opinion for TEGSEDI [media release]. June 1 2018.Google Scholar
- 5.European Medicines Agency. Tegsedi (inotersen): summary of product characteristics. 2018. http://www.ema.europa.com. Accessed 18 July 2018.
- 6.Ionis Pharmaceuticals. Ionis’ inotersen NDA accepted for priority review by the FDA [media release]. Jan 8 2018.Google Scholar
- 7.Ionis Pharmaceuticals. Ionis and Akcea partner to commercialize inotersen for hATTR [media release]. March 15 2018.Google Scholar
- 8.Ionis Pharmaceuticals. Ionis to independently advance inotersen and IONIS-FB-L Rx [media release]. Aug 11 2017.Google Scholar
- 9.Ionis Pharmaceuticals. Isis Pharmaceuticals changes name to Ionis Pharmaceuticals [media release]. Dec 18 2015.Google Scholar
- 10.Guo S, Ackermann E, Booten S, et al. Clinical development of an antisense therapy for the treatment of transthyretin amyloidosis [abstract no. M841]. Ann Neurol. 2011;70(Suppl 15):S86.Google Scholar
- 12.Brannagan T, Wang AK, Coelho T, et al. Open label extension of the phase 3 study NEURO-TTR to assess the long-term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis [abstract no. P1.324]. Neurology. 2018;90(15 Suppl).Google Scholar
- 13.Ionis Pharmaceuticals, Akcea Therapeutics. Ionis and Akcea present new data from ATTR amyloidosis program at 16th International Symposium on Amyloidosis [media release]. March 26 2018.Google Scholar