Background: Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the () gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype.
Objective: To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN).
Methods: Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures.
Results: Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted.
Conclusion: The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997406 | PMC |
| http://dx.doi.org/10.1055/s-0044-1781463 | DOI Listing |
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- - The phase 3 NEURO-TTRansform trial demonstrated that eplontersen significantly reduced transthyretin (TTR) levels and halted the progression of neuropathy impairment in patients with hereditary TTR-mediated amyloidosis after 65 weeks of treatment.
- - The study involved patients initially receiving inotersen, who then switched to eplontersen, resulting in a greater reduction of TTR levels and stabilized quality of life and nutritional status during the eplontersen treatment.
- - Patients who switched to eplontersen experienced fewer treatment-emergent adverse events, restored platelet counts, and overall better tolerability, indicating a favorable benefit-risk profile for this treatment strategy. *
Article Synopsis
- Hereditary transthyretin amyloidosis (ATTR) is a serious genetic disorder caused by a mutation in the transthyretin gene, leading to harmful misfolding and buildup of amyloid in organs, resulting in severe nerve and heart issues.
- Existing treatments like liver transplantation and stabilizers have limitations, but RNA interference (RNAi) has emerged as a promising new approach, with the drug patisiran introduced in 2018 showing significant potential.
- The study reviews various RNAi-based therapies for ATTR, including patisiran, vutrisiran, inotersen, and eplontersen, focusing on their effects on patients' quality of life,
Article Synopsis
- Hereditary transthyretin amyloidosis (ATTRv) and wild-type ATTR amyloidosis (ATTRwt) are rare and progressive disorders characterized by the accumulation of amyloid fibrils in various organs, leading to significant health complications and unmet medical needs for patients.
- The Amyloidosis Forum, a partnership between the FDA and the Amyloidosis Research Consortium, recently discussed strategies for advancing drug development and clinical trial designs for ATTR amyloidosis, considering perspectives from various stakeholders.
- With the changing landscape of ATTR amyloidosis, reliance on historical control data is diminishing, highlighting the importance of using contemporary real-world data to inform clinical trial designs and address relevant clinical questions effectively.
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