Drug updated on 10/29/2024
| Dosage Form | Injection (subcutaneous; 284 mg/1.5 mL) |
| Drug Class | Transthyretin-directed antisense oligonucleotides |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
Latest News
Summary
- This summary is based on the review of five systematic review(s)/meta-analysis(es). [1-5]
- Neuropathy and Quality of Life Outcomes: Inotersen significantly reduces plasma TTR levels and improves neuropathy and quality of life compared to placebo, while patisiran also shows significant improvements in these outcomes. Tafamidis demonstrates a slight reduction in the progression of peripheral neuropathy compared to placebo.
- Cardiovascular Outcomes: Tafamidis significantly improves all-cause mortality and cardiovascular hospitalizations and reduces worsening in cardiovascular-related functional assessments compared to placebo. Inotersen showed conflicting results regarding cardiac imaging parameters.
- Comparative Effectiveness: Tafamidis, patisiran, and inotersen demonstrated significant benefits for TTR-related amyloid polyneuropathy in high-quality RCTs, with patisiran and inotersen noted for reducing the progression of peripheral neuropathy and improving quality of life more than placebo, while tafamidis was beneficial in reducing peripheral neuropathy progression but less effective in improving quality of life compared to patisiran.
- Safety Concerns for Inotersen: Inotersen may slightly increase mortality and the occurrence of severe adverse events compared to placebo, with more dropouts due to adverse events observed in the inotersen group.
- Safety Profiles of Other Treatments: Tafamidis and diflunisal showed no significant increase in severe adverse events or mortality compared to placebo, while patisiran exhibited a relatively safer profile with fewer dropouts due to adverse events compared to placebo.
- Population Types and Subgroup Considerations: Patisiran demonstrated efficacy in improving neuropathy and quality of life in a subgroup of patients with variant transthyretin cardiac amyloidosis (CA), while tafamidis and patisiran were evaluated for both variant and wild-type transthyretin CA. Inotersen did not have specific population types or subgroups highlighted in the reviewed studies.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Tegsedi (inotersen) Prescribing Information. | 2024 | Sobi, Inc., Waltham, MA |
Systematic Reviews / Meta-Analyses
| Document Title | Year | Source |
|---|---|---|
| Targeting transthyretin - Mechanism-based treatment approaches and future perspectives in hereditary amyloidosis | 2021 | Journal of Neurochemistry |
| Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome' | 2021 | Journal of Neuromuscular Diseases |
| Specific Therapy for Transthyretin Cardiac Amyloidosis: A Systematic Literature Review and Evidence-Based Recommendations | 2020 | Journal of the American Heart Association |
| Pharmacological treatment for familial amyloid polyneuropathy | 2020 | The Cochrane Database of Systematic Reviews |
| The impact of clinical heterogeneity on conducting network meta-analyses in transthyretin amyloidosis with polyneuropathy | 2020 | Current Medical Research and Opinion |
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Canadian Guidelines for Hereditary Transthyretin Amyloidosis Polyneuropathy Management | 2022 | The Canadian Journal of Neurological Sciences |
| Diagnosis and screening of patients with hereditary transthyretin amyloidosis (hATTR): current strategies and guidelines. | 2020 | Therapeutics and Clinical Risk Management |