Open-label Study of Patisiran in Patients with hATTR Amyloidosis Post-Orthotopic Liver Transplant
Teresa Coelho1, Julian Gillmore2, David Adams3, Francisco Muñoz-Beamud4, Anna Mazzeo5, Jonas Wixner6, Violaine Planté-Bordeneuve7, Laura Lladó8, Seth Arum9, Jing Jing Wang9, Xingyu Li9
1Unidate Clinica de Paramoloidose Hospital, 2UCL, 3APHP, 4Juan Ramón Jiménez Hospital, 5University of Messina, 6Umeå University, 7University Hospital Henri Mondor, 8Hospital Universitari de Bellvitge, 9Alnylam Pharmaceuticals
Objective:
To describe the efficacy, safety, and PK of patisiran in hATTR amyloidosis with polyneuropathy patients with disease progression post-OLT.
Background:
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, life-threatening disease. Orthotopic liver transplant (OLT) suppresses mutant transthyretin (TTR) production to slow progression in early disease. Patisiran suppresses production of mutant and wild-type TTR and has been shown to halt or reverse polyneuropathy and improve quality of life in patients in APOLLO.
Design/Methods:
Phase 3b open-label study (NCT03862807) to evaluate the safety, efficacy, and pharmacokinetics (PK) of patisiran in patients with hATTR amyloidosis with polyneuropathy and disease progression post-OLT. Patients receive patisiran 0.3 mg/kg intravenously once every 3 weeks for 12 months. 6-month safety and efficacy analyses will be presented at the congress.
Results:
23 patients were enrolled and received patisiran in the study. Median age was 58.0 years, 13 (56.5%) were males, and 15 (65.2%) had V30M mutation. At baseline, 1 (4.3%) patient had polyneuropathy disability (PND) score I, 9 (39.1%) had PND II, and 13 (56.5%) had PND IIIA/B. Five patients (21.7%) had New York Heart Association (NYHA) classification I, 5 (21.7%) had NYHA II, and none had NYHA III or IV at study baseline. The mean (SD) percent change in TTR at week 3 was -81.9% (11.3). Twenty-one (91.3%) patients experienced at least one adverse event (AE) and 3 (13.0%) patients experienced at least one serious AE. Five (21.7%) patients had AEs that were considered related to treatment. Updated 6-month efficacy and safety data will be presented at the congress.
Conclusions:
This study will continue to investigate the efficacy, safety, and PK of patisiran with the potential to address an unmet need in hATTR amyloidosis with polyneuropathy patients with disease progression post-OLT.