Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial

Abstract

Objective

Assess how baseline polyneuropathy severity impacts response to patisiran regarding neurologic impairment and quality of life (QOL) in patients with hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis).

Methods

This post hoc analysis grouped patients from the Phase 3 APOLLO study (n = 225) by baseline Neuropathy Impairment Score (NIS) into quartiles: 6–<31; 31–<57; 57–<85.5; 85.5–141.6. Neurologic impairment (modified NIS+7 [mNIS+7], NIS total score), disability (Rasch-built Overall Disability Scale [R-ODS]), gait speed (10-meter walk test [10-MWT]), grip strength, and QOL (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN] questionnaire) were assessed.

Results

Across all baseline NIS quartiles, patisiran improved several clinical markers of disease compared with placebo at 18 months. Patients in lower NIS quartiles, treated with patisiran earlier in the disease course, maintained better scores in mNIS+7, NIS total score, R-ODS, 10-MWT, grip strength, and Norfolk QOL-DN versus those in higher NIS quartiles, while placebo-treated patients experienced worsening of all functional measures after 18 months across all quartiles.

Conclusions

Patisiran treatment improved neurologic function and QOL across a wide range of baseline polyneuropathy severities versus placebo. Timing of treatment initiation in patients with ATTRv amyloidosis remains critical for the preservation of function.

(ClinicalTrials.gov number, NCT01960348)

Keywords:

• ATTRv amyloidosis
• hereditary transthyretin-mediated (hATTR) amyloidosis
• patisiran
• polyneuropathy
• RNA interference

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Acknowledgments

The authors thank the patients, their families, investigators, study staff, and collaborators involved in the APOLLO study for their valued contribution to this study. They would also like to thank Rebecca Shilling for her contribution to the study and manuscript content.

Disclosure statement

Dianna Quan reports research funding from Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Apellis, Argenx, Cytokinetics, Ionis Pharmaceuticals, Momenta, Pfizer, and Viela, consulting fees from Alnylam Pharmaceuticals, and investigator meeting expenses from Pfizer.

Laura Obici reports support for conducting clinical trials and manuscript preparation funded by Alnylam Pharmaceuticals, and speaker honoraria from Akcea Therapeutics, Alnylam Pharmaceuticals, and Pfizer.

John L. Berk reports support as a study investigator and coordinator from Alnylam Pharmaceuticals and Pfizer, fees for scientific advisory board attendance from Corino Therapeutics and Intellia Therapeutics, fees for participating in ad hoc advisory committees for Akcea Therapeutics and Ionis Pharmaceuticals, and fees for a visiting professor presentation by Alnylam Pharmaceuticals.

Yukio Ando reports speaker honoraria from Pfizer.

Emre Aldinc and Matthew T. White are employees of Alnylam Pharmaceuticals and hold shares in Alnylam Pharmaceuticals.

David Adams reports consulting fees from Alnylam Pharmaceuticals and Pfizer, and support for participation in clinical trials funded by Alnylam Pharmaceuticals and Ionis Pharmaceuticals.

Additional information

Funding

This study was funded by Alnylam Pharmaceuticals, USA. Editorial support was provided by Amy-Leigh Johnson, PhD, of Adelphi Communications Ltd, Macclesfield, UK, in accordance with the Good Publication Practice (GPP3) guidelines, funded by Alnylam Pharmaceuticals.