High-risk Thrombophilia predict early thrombosis recurrence in acute non-cirrhotic portal vein thrombosis related to local factors: LOCAPORT

Method: ENVISION is a phase 3, randomised, placebo-controlled trial in patients ≥12 years old with AHP who had experienced ≥2 attacks requiring hospitalization, urgent care, or intravenous hemin at home in the past 6M, with a 6M double-blind (DB) period followed by a 30M OLE period.Results: Of 94 patients enrolled, 93 patients entered the OLE period.Givosiran treatment led to sustained lowering of median urinary ALA to near-normal levels and to lowering of PBG levels by >90% in the continuous givosiran and placebo crossover groups at 36M.Continued givosiran treatment also led to a sustained reduction in attacks and hemin use in both groups.The proportion of patients with 0 attacks per 3 M interval improved over the OLE period, with 86% of patients in the continuous givosiran group and 92% of patients in the placebo crossover group attack-free at 33-36 M. Similarly, the proportion of patients with 0 days of hemin use improved over the OLE period, with no days of hemin use in 88% of patients in the continuous givosiran group and 90% of patients in the placebo crossover group at 33-36 M. Exploratory measures showed further improvements in quality of life and activities of daily living during the OLE versus the DB period (Short Form 12-Item Health Survey, EuroQol visual analogue scale, and Porphyria Patient Experience Questionnaire).Most common treatment-related adverse events (AEs) (>10%) were injection-site reactions (ISRs), nausea, and fatigue.Six patients discontinued study drug due to AEs; 4 of these patients discontinued due to treatment-related AEs.Conclusion: Long-term givosiran treatment provides sustained benefit to patients with AHP, maintaining reduced frequency of attacks and hemin use and further improving physical functioning and quality of life.Most common treatment-related AEs were ISRs, nausea, and fatigue.