HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
Summary
The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02) in participants with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will receive vutrisiran subcutaneous (SC) injection once every 3 months (q3M) or the reference comparator patisiran intravenous (IV) injection once every 3 weeks (q3w) during the 18 month Treatment Period. This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints during the 18 Month Treatment Period. Following the 18 Month Treatment Period, all participants will be randomized to receive vutrisiran 50 mg SC injection once every 6 months (q6M) or vutrisiran 25 mg q3M in the Randomized Treatment Extension (RTE) Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.
Timeline
- Start
- 2019-02-14
- Primary completion
- 2020-11-10
- Completion
- 2025-11-05
Outcome
Met primary endpoint
paper Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10-12) PMID 35875890 ↗
registry p <0.0000001; LS Mean Difference -17.00 (95% CI -21.78 to -12.22) NCT03759379 ↗
release “At 9 months, vutrisiran met the primary and all secondary endpoints in HELIOS-A, specifically:” alnylam.com ↗
release “As reported previously, positive results were achieved in HELIOS-A with a 25 mg quarterly dosing regimen of subcutaneously administered vutrisiran;” alnylam.com ↗
release “The HELIOS-A study included 164 hATTR amyloidosis patients with polyneuropathy. At 9 months, vutrisiran met the primary and all secondary endpoints” alnylam.com ↗
release “Alnylam previously announced that HELIOS-A met its primary and secondary endpoints at 9 months” alnylam.com ↗
release “Alnylam previously announced that vutrisiran met its primary endpoint and all secondary endpoints at nine months in HELIOS-A” alnylam.com ↗
release “Vutrisiran met the primary and all secondary endpoints of the study at both 9 months and 18 months” alnylam.com ↗
release “HELIOS-A Phase 3 study evaluating a biannual dosing regimen of vutrisiran. Non-inferiority of 50 mg biannual (vs. 25 mg quarterly) was established” alnylam.com ↗
Publications
- Cauquil C, Adams D, Gillmore J, Gonzalez-Duarte A, Mezei M, Obici L, Sekijima Y, Zhao W, Boyle K, Badri P, Sweetser M, Moffitt C, Waddington-Cruz M. Long-term efficacy and safety of vutrisiran in hereditary transthyretin amyloidosis with polyneuropathy: final analysis of the HELIOS-A randomized treatment extension. Amyloid. 2026 Jun 15:1-12. doi: 10.1080/13506129.2026.2685666. Online ahead of print.
- Luigetti M, Quan D, Berk JL, Conceicao I, Misumi Y, Chao CC, Bender S, Aldinc E, Vest J, Adams D. Impact of Baseline Neuropathy Severity on Vutrisiran Treatment Response in the Phase 3 HELIOS-A Study. Neurol Ther. 2024 Jun;13(3):625-639. doi: 10.1007/s40120-024-00595-9. Epub 2024 Mar 21.
- Obici L, Ajroud-Driss S, Lin KP, Berk JL, Gillmore JD, Kale P, Koike H, Danese D, Aldinc E, Chen C, Vest J, Adams D; HELIOS-A Collaborators Study Group. Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy. Neurol Ther. 2023 Oct;12(5):1759-1775. doi: 10.1007/s40120-023-00522-4. Epub 2023 Jul 31.
- Adams D, Tournev IL, Taylor MS, Coelho T, Plante-Bordeneuve V, Berk JL, Gonzalez-Duarte A, Gillmore JD, Low SC, Sekijima Y, Obici L, Chen C, Badri P, Arum SM, Vest J, Polydefkis M; HELIOS-A Collaborators. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023 Mar;30(1):1-9. doi: 10.1080/13506129.2022.2091985. Epub 2022 Jul 23.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Patisiran | Small interfering RNA (siRNA) | 0.3 mg/kg | Intravenous |
| Subject | Vutrisiran | Small interfering RNA (siRNA) | 25 mg | Subcutaneous |
| Subject | Vutrisiran | Small interfering RNA (siRNA) | 50 mg | Subcutaneous |