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Patisiran, an RNAi therapeutic for hereditary transthyretin-mediated amyloidosis: Sub-analysis in Taiwanese patients from the APOLLO study

Authors :
Kon-Ping Lin
Chih-Chao Yang
Yi-Chung Lee
Ming-Jen Lee
John Vest
Marianne T. Sweetser
Matthew T. White
Prajakta Badri
Sung-Tsang Hsieh
Chi-Chao Chao
Source :
Journal of the Formosan Medical Association, Vol 123, Iss 9, Pp 975-984 (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Background: To examine the efficacy and safety of patisiran, an RNA interference therapeutic, in patients from Taiwan with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy. Methods: The APOLLO phase 3 trial included patients from Taiwan who received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks (q3w) for 18 months (18 M), followed by patisiran 0.3 mg/kg q3w in an ongoing global open-label extension (OLE) study. The primary endpoint was change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 18 M. Results: Eighteen Taiwanese patients were enrolled in APOLLO (patisiran, n = 8; placebo, n = 10; all A97S gene variant) and 14 continued in the global OLE. In this Taiwanese sub-population, beneficial treatment effects at 18 M were observed in mNIS+7 (least squares mean difference in change from baseline [patisiran-placebo], −26.5 points; 95% confidence interval: −45.5, −7.5). Patients who switched from placebo to patisiran demonstrated slowing of polyneuropathy progression at month 12 in the global OLE, while those who received patisiran in APOLLO maintained the beneficial treatment effects. Patisiran had an acceptable safety profile in the Taiwanese sub-population. Conclusion: This analysis suggests that patisiran is well tolerated and may provide a substantial clinical benefit for Taiwanese patients with hATTR amyloidosis with polyneuropathy. Trial registration information: The studies were registered on the ClinicalTrials.gov. The APOLLO study ClinicalTrials.gov identifier is NCT01960348 (https://clinicaltrials.gov/ct2/show/NCT01960348), with the registration date of October 10, 2013, and the first patient was enrolled on December 13, 2013. For the global OLE, the ClinicalTrials.gov identifier is NCT02510261 (https://clinicaltrials.gov/ct2/show/NCT02510261) with the registration date of July 29, 2015, and the first patient was enrolled on July 13, 2015. Classification of evidence: This study provides Class II evidence that treatment with patisiran is safe and efficacious in Taiwanese patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy.

Details

Language :
English
ISSN :
09296646
Volume :
123
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Journal of the Formosan Medical Association
Publication Type :
Academic Journal
Accession number :
edsdoj.b5699cac1045209b1a2938728fe680
Document Type :
article
Full Text :
https://doi.org/10.1016/j.jfma.2024.03.008