Publications

The material below is provided to support scientific exchange. Any content about investigational therapeutics or investigational uses of locally approved products does not establish the safety or efficacy of these therapeutics or uses, and there is no guarantee of local regulatory approval.

For questions beyond a product’s authorized indications or for information not available here, please contact Alnylam Medical Information.

Effectiveness of patisiran after switching from tafamidis for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy

Publication Details

Journal of the American College of Cardiology

August 2025

Access Here

Author(s)

Celine Labeyrie¹, Madeline Merkel², Sakshi Sethi³, Lyuba Popadic³, Hongbo Yang³, Marianne T Sweetser², Hollis Lin², David Adams¹

Affiliations

¹Neurology Department, Assistance Publique-Hopitaux de Paris (AP-HP), CERAMIC, Centre Hospitalier Universitaire (CHU) Bicêtre, INSERM U1195, Université Paris-Saclay, Le Kremlin-Bicêtre, France; 2Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA;³Analysis Group, Boston, Massachusetts, USA

Abstract

Background and purpose

Hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN [v for variant]) is a rare, progressive disease associated with multisystemic impairments. This study assessed the real-world outcomes of patients with ATTRv-PN who switched from tafamidis to patisiran, as well as the reasons for the treatment switch.

Objectives:

The purpose of this study was to investigate associations of echocardiographic measures of cardiac structure and function with the primary outcome and to assess whether favorable changes in cardiac structure and function with vutrisiran were associated with improvements in outcomes.

Methods:

This was a retrospective chart review study at a large expert referral center. Data were extracted from medical charts of patients with ATTRv-PN who switched from tafamidis to patisiran on or before 30 August 2019. Data elements included demographic and clinical characteristics, rationale for switch, and disease measures evaluated from tafamidis initiation through the 12-month patisiran treatment period.

Results:

Among the 24 patients with ATTRv-PN included in the study, 50.0% had a V30M variant, and the mean (SD) age was 67.3 (8.0) years. During tafamidis treatment (mean [SD] = 30.1 [17.5] months) before switching to patisiran, patients worsened across multiple polyneuropathy measures, including walking ability, Neuropathy Impairment Score, and autonomic function. Neuropathic disease progression on tafamidis was the principal reason for switching to patisiran. After 12 months on patisiran (mean [SD] = 11.7 [1.4] months), patients experienced attenuated disease progression or improvement in the aforementioned measures of polyneuropathy..

Conclusions:

Switching from tafamidis to patisiran attenuated the rate of functional decline, and most patients experienced stabilization or improvement of at least one polyneuropathy measure within 12 months of patisiran treatment. Timely switch from tafamidis to patisiran can be beneficial to avoid rapid disease progression in patients with ATTRv-PN.