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

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive and fatal disease. Patisiran is an RNA interference therapeutic that inhibits synthesis of disease-causing mutant and wild-type transthyretin (TTR) protein in hATTR amyloidosis. Aim: The efficacy and safety of patisiran were evaluated in the Phase 3 APOLLO study in patients with hATTR amyloidosis with polyneuropathy. Methods: In total, 225 patients from 19 countries, including Japan (n = 16), received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks for 18 months. Patisiran halted or improved outcomes of polyneuropathy (measured by modified Neuropathy Impairment Score +7 [mNIS+7]) and improved quality of life (QOL) (measured by Norfolk Quality of Life-Diabetic Neuropathy questionnaire). Present analyses assess the efficacy, safety, pharmacokinetic exposure, and pharmacodynamic effect of patisiran in the Japanese sub-population of APOLLO. Results: Consistent with the overall APOLLO population, patisiran significantly improved outcomes of polyneuropathy (mNIS+7) compared with placebo at 18 months in the APOLLO Japanese patients. Patisiran treatment also demonstrated benefit in QOL, motor strength, gait speed, nutritional status, and autonomic symptoms compared with placebo at 18 months in the Japanese sub-population. Patisiran was generally well tolerated in Japanese patients, with most adverse events mild or moderate; safety profile was similar to the overall APOLLO population, and no deaths were observed. Patisiran pharmacokinetic exposures and TTR reduction were comparable to the overall population. Conclusions: Data in the Japanese sub-population were consistent with those from the overall APOLLO population and indicate a notable health benefit for patisiran treatment in Japanese patients with hATTR amyloidosis with polyneuropathy.