Acute hepatic porphyria (AHP) is a family of rare genetic diseases due to enzyme defects in hepatic heme biosynthesis. ENVISION is an ongoing phase 3 study, evaluating efficacy and safety of givosiran in symptomatic AHP patients.

Describe efficacy and safety resuts of the ENVISION 18-month OLE period.

Exploratory efficacy (composite porphyria attacks, ALA/PBG levels, hemin use, and missed days of work) and safety measures in the OLE were assessed. Analyses were descriptive and represent the timepoint after which all patients completed at least their Month 18 visit (01/10/2020).

Ninety-four patients completed the DB period, and 93 patients entered the OLE (placebo/givosiran = 46; givosiran/givosiran = 47). Mean exposure to givosiran was 12.97 [SD = 3.6] months for placebo/givosiran and 18.86 [3.6] months for givosiran/givosiran, with maximum exposure of 25.1 months. Continued treatment in givosiran/givosiran patients led to a median annualized attack rate (AAR) of 0.58 (range: 0–16.2) through Month 18. Patients in the placebo/givosiran group had an AAR of 1.62 (range: 0–11.8) after receiving givosiran for ≥12 months during the OLE period, compared with 10.65 (range: 0–51.6) whilst receiving placebo during the 6-month DB period. Sustained ALA/PBG lowering during the OLE was accompanied by sustained reductions in hemin use, and more than half of the placebo/givosiran patients experienced 0 days of hemin use. There was a decrease in the number of work days missed in the past 4 weeks at Month 6 (mean = 6.7 days [SD = 7.8], n = 20/46) compared with Month 18 (2.5 [5.1], n = 23/46), for patients in the placebo/givosiran group who were able to work. The most common related adverse events (AEs) observed during givosiran treatment were injection site reactions, nausea and fatigue. Hepatic and renal AEs were both reported in 17% of patients each during givosiran treatment. No new safety concerns occurred in the OLE period.

In the ongoing OLE period of the ENVISION study, patients receiving long-term treatment with givosiran demonstrated a durable response in clinical efficacy, across a wide range of clinical parameters. Following the initial 6 months of givosiran treatment during the OLE, placebo/givosiran patients had a similar clinical response to that observed in givosiran/givosiran patients in the OLE period through Month 18. The safety profile of givosiran remained acceptable and consistent with that previously observed.