ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
Summary
The purpose of this study is to evaluate the effect of subcutaneous givosiran (ALN-AS1), compared to placebo, on the rate of porphyria attacks in patients with Acute Hepatic Porphyrias (AHP).
Timeline
- Start
- 2017-11-16
- Primary completion
- 2019-01-31
- Completion
- 2021-05-31
Outcome
Met primary endpoint
registry analysis (superiority test); Placebo vs Givosiran 2.5 mg/kg; p <0.0001; Rate ratio 0.26 (95% CI 0.16 to 0.41) NCT03338816 ↗
release “givosiran met the primary endpoint of reduction in the annualized rate of composite porphyria attacks relative to placebo” alnylam.com ↗
release “In the ENVISION study, patients receiving givosiran had a 74 percent mean reduction in the annualized rate of composite porphyria attacks compared to placebo” alnylam.com ↗
release “In the pivotal ENVISION Phase 3 study, givosiran was shown to significantly reduce the annualized rate of composite porphyria attacks” alnylam.com ↗
release “In the pivotal ENVISION Phase 3 study, givosiran was shown to significantly reduce the annualized rate” alnylam.com ↗
Publications
- Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.
- Lee MJ, Kuo HC, Chou LN, Sweetser MT, Wang JD. A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort. J Formos Med Assoc. 2024 Jun;123(6):679-686. doi: 10.1016/j.jfma.2023.10.016. Epub 2023 Dec 2.
- Kuter DJ, Bonkovsky HL, Monroy S, Ross G, Guillen-Navarro E, Cappellini MD, Minder AE, Hother-Nielsen O, Ventura P, Jia G, Sweetser MT, Thapar M; ENVISION Investigators. Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial. J Hepatol. 2023 Nov;79(5):1150-1158. doi: 10.1016/j.jhep.2023.06.013. Epub 2023 Jul 20.
- Wang B, Ventura P, Takase KI, Thapar M, Cassiman D, Kubisch I, Liu S, Sweetser MT, Balwani M. Disease burden in patients with acute hepatic porphyria: experience from the phase 3 ENVISION study. Orphanet J Rare Dis. 2022 Aug 26;17(1):327. doi: 10.1186/s13023-022-02463-x.
- Balwani M, Sardh E, Ventura P, Peiro PA, Rees DC, Stolzel U, Bissell DM, Bonkovsky HL, Windyga J, Anderson KE, Parker C, Silver SM, Keel SB, Wang JD, Stein PE, Harper P, Vassiliou D, Wang B, Phillips J, Ivanova A, Langendonk JG, Kauppinen R, Minder E, Horie Y, Penz C, Chen J, Liu S, Ko JJ, Sweetser MT, Garg P, Vaishnaw A, Kim JB, Simon AR, Gouya L; ENVISION Investigators. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Engl J Med. 2020 Jun 11;382(24):2289-2301. doi: 10.1056/NEJMoa1913147.