Impact of patisiran on polyneuropathy of hereditary transthyretin amyloidosis in patients with a V122I or T60A variant: a phase IV multicenter study

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. 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 <i>vs</i>. baseline. Safety was monitored throughout the trial. 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 <i>vs</i>. 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. Patisiran demonstrated a consistent positive effect across multiple endpoints in patients with V122I/T60A ATTRv amyloidosis, including polyneuropathy manifestations.