S1154 Clinical Outcomes in Patients With Acute Hepatic Porphyria Treated With Givosiran Who Stopped Hemin Prophylaxis at Study Entry: A Post Hoc Analysis of Data From the Phase 3 ENVISION Study Through Month 12

Abstract

INTRODUCTION: Acute Hepatic Porphyria (AHP) is a family of rare genetic diseases due to enzyme defects in heme synthesis in the liver. Accumulation of toxic heme intermediates ALA and PBG may result in neurovisceral attacks and chronic manifestations. Intravenous (IV) hemin is approved to treat acute attacks and is sometimes used off-label prophylactically. In the ENVISION study in AHP patients, givosiran, an RNAi therapeutic, reduced the composite porphyria annualized porphyria attack rate (AAR) vs. placebo (pbo). A post-hoc analysis was conducted to evaluate outcomes in AHP patients with or without prior hemin prophylaxis prior to screening. METHODS: ENVISION (NCT03338816) is an ongoing Phase 3 global, randomized, pbo-controlled study, evaluating givosiran efficacy and safety in symptomatic AHP patients in a 6-month double blind (DB) period and an open label extension (OLE) period (30 months). Patients were required to discontinue prophylactic hemin treatment at study entry, but could receive hemin for acute attacks. Outcome measures included the composite porphyria AAR (defined as attacks requiring hospitalization, urgent care, or IV hemin at home). Analyses were descriptive. RESULTS: For AHP patients on prior hemin prophylaxis (median historical AAR: 9.0), a 77% reduction in mean AAR was observed with givosiran treatment vs. pbo in the DB period (Table 1). A similar reduction (63%) in mean AAR was observed in those without prior hemin prophylaxis (median historical AAR: 7.0). In both groups, further reduction in AAR was observed in patients who continued on givosiran in the OLE period (Table 1). A similar reduction in AAR was also observed in both groups of pbo patients who received givosiran in the OLE (Table 1). The percentage of patients with 0 composite attacks increased in each group following 6-months of givosiran treatment in the OLE with 55% and 67% in the patients who had continued givosiran treatment (Table 1). Additional analyses of outcome measures between the two groups will be presented. CONCLUSION: Clinically meaningful reduction in the AAR was observed in AHP patients treated with givosiran regardless of whether they received hemin prophylaxis prior to study entry, with further AAR reduction observed in those who continued to receive givosiran during the OLE. In addition, a similar benefit was observed in pbo patients who received givosiran for 6-months during the OLE period regardless of prior hemin prophylaxis use.Table 1