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Impact of Patisiran on Polyneuropathy of Hereditary Transthyretin Amyloidosis in Patients with a V122I or T60A Variant: A Phase IV Multicenter Study

Publication Details

Annals of Medicine

September 2025

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Author(s)

Yessar Hussain¹, Saurabh Malhotra², Brett W Sperry³, Francy Shu⁴, Karthikeyan Ananthasubramaniam⁵, Urvi Desai⁶, Ugochukwu Egolum⁷, Joel Fernandez⁸, Miriam Freimer⁹, Elizabeth Mauricio¹⁰, Dianna Quan¹¹, Roy Small¹², Kelley Capocelli¹³, Steven Roblin¹³, Shaun Bender¹³, Patrick Y Jay¹³, Elena Yureneva¹³, Ronald Zolty¹⁴

Affiliations

¹Austin Neuromuscular Center, Austin, TX, USA; ²Division of Cardiology, Cook County Health and Rush Medical College, Chicago, IL, USA; ³Department of Cardiovascular Medicine, Saint Luke's Mid America Heart Institute, Kansas City, MO, USA; ⁴Department of Neuroscience, Baylor University Medical Center/Baylor Scott and White Health, Dallas, TX, USA; ⁵Department of Cardiology, Henry Ford West Bloomfield Hospital, West Bloomfield Township, MI, USA; ⁶Department of Neurology, Atrium Health Wake Forest University, Charlotte, NC, USA; ⁷Northeast Georgia Medical Center, Division of Cardiology, Georgia Heart Institute, Gainesville, GA, USA; ⁸Department of Cardiovascular Services, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; ⁹Department of Neurology, Wexner Medical Center, Ohio State University, Columbus, OH, USA; ¹⁰Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; ¹¹Department of Neurology, University of Colorado Anschutz, Aurora, CO, USA; ¹²Department of Cardiology, Lancaster General Health/Penn Medicine, Lancaster, PA, USA; ¹³Alnylam Pharmaceuticals, Cambridge, MA, USA; ¹⁴Department of Cardiology, University of Nebraska Medical Center, Omaha, NE, USA

Abstract

Background:

This study assessed the effectiveness and safety of patisiran in patients with V122I/T60A variant transthyretin (ATTRv) amyloidosis with polyneuropathy. These variants have been under-represented in previous trials of gene-silencing agents.

Methods:

This was a multicenter, phase IV study conducted at 27 sites in the USA. Patients were ≥ 18 years, diagnosed with ATTRv amyloidosis with polyneuropathy and a documented V122I or T60A variant. Patisiran-treated patients were enrolled prospectively, ambispectively, and retrospectively. The primary endpoint was the proportion of patients with a stable or improved polyneuropathy disability (PND) score at 12 months vs. baseline. Safety was monitored throughout the trial.

Results:

Sixty-seven patients were enrolled, of whom 58 received ≥ 1 dose of patisiran. In the efficacy population, 42/45 (93.3%) patients demonstrated stable or improved PND scores from baseline to Month 12. Patients also showed stable or improved quality of life, health status, autonomic symptoms, and cardiac function vs. baseline. Adverse events occurred in 13/42 (31.0%) patients in the prospective and ambispective cohorts; most were mild or moderate. No deaths or cardiac hospitalizations were considered related to patisiran.

Conclusions:

Patisiran demonstrated a consistent positive effect across multiple endpoints in patients with V122I/T60A ATTRv amyloidosis, including polyneuropathy manifestations.