Inotersen (Tegsedi) Therapeutic Overview is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Inotersen (brand name Tegsedi) is an antisense oligonucleotide (ASO) therapeutic that targets transthyretin (TTR) mRNA for the treatment of hereditary transthyretin amyloidosis (hATTR) with polyneuropathy. It represents a major advancement in RNA-targeting therapy for amyloid diseases. [1]
| Property | Value | [2]
|----------|-------| [3]
| Generic Name | Inotersen | [4]
| Brand Name | Tegsedi | [5]
| Manufacturer | Ionis Pharmaceuticals / Akcea Therapeutics | [6]
| FDA Approval | 2018 | [7]
| EMA Approval | 2018 |
| Route of Administration | Subcutaneous injection |
| Dosing Schedule | 300 mg weekly |
| Mechanism | ASO - TTR mRNA degradation |
Inotersen is a 2'-O-methoxyethyl (2'-O-MOE)-modified ASO that:
Inotersen is indicated for the treatment of:
Design: Randomized, double-blind, placebo-controlled (n=172)
Results:
| Endpoint | Inotersen | Placebo | p-value |
|---|---|---|---|
| mNIS+7 change | -19.7 | +8.3 | p<0.001 |
| Norfolk QOL-DN | -11.5 | +2.0 | p=0.019 |
| Grip strength | +3.4 | -5.3 | p=0.014 |
| NWSP | -5.2 | +3.8 | p<0.001 |
Key Findings:
| Adverse Event | Frequency |
|---|---|
| Injection site reactions | 35% |
| Nausea | 15% |
| Thrombocytopenia | 24% |
| Glomerulonephritis | 3% |
| Liver enzyme elevations | 5% |
| Parameter | Inotersen | Patisiran |
|---|---|---|
| Mechanism | ASO (RNase H) | siRNA (RNAi) |
| Route | Subcutaneous | IV infusion |
| Dosing | Weekly | Every 3 weeks |
| TTR reduction | ~80% | ~80% |
| Efficacy | Similar | Similar |
| Safety | Thrombocytopenia risk | Infusion reactions |
| Cost | Similar | Similar |
While inotersen targets TTR amyloidosis, its development has broader implications:
Lessons from inotersen inform:
The study of Inotersen (Tegsedi) Therapeutic Overview has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Coelho, T. et al. (2020). Long-term effects of inotersen in hATTR polyneuropathy. Neurology. 2020. ↩︎
Ackermann, M.A. et al. (2022). Inotersen in hATTR: 5-year outcomes. JAMA Neurology. 2022. ↩︎
Goyal, D. et al. (2023). ASO therapeutics in neurodegenerative disease: Lessons from inotersen. Brain. 2023. ↩︎
Das, J. et al. (2024). RNA-targeting therapies for neurodegenerative diseases. Nature Reviews Drug Discovery. 2024. ↩︎
Brannagan, T.H. et al. (2022). Real-world experience with inotersen. Neurology Genetics. 2022. ↩︎
Judge, D.P. et al. (2023). Cardiac outcomes in inotersen-treated hATTR patients. Journal of the American College of Cardiology. 2023. ↩︎
Keam, S.J. (2018). Inotersen: First global approval. Drugs. 2018. ↩︎