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Recent well designed trials have consolidated the place of tacrolimus as an important choice for primary immunosuppression in solid organ transplantation and in BMT. Notably, in adults and children receiving transplants, tacrolimus-based primary immunosuppression was at least as effective or provided better efficacy than cyclosporin microemulsion treatment in terms of patient and graft survival, treatment failure and the incidence of acute and corticosteroid-resistant rejection episodes. The reduced incidence of rejection episodes in renal transplant recipients receiving tacrolimus translated into a better cost effectiveness relative to cyclosporin microemulsion treatment. The optimal immunosuppression regimen is ultimately dependent on balancing such factors as the efficacy of the individual drugs, their tolerability, potential for drug interactions and pharmacoeconomic issues.

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.