Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study

作者：Eliane Sardh, Manisha Balwani, David C. Rees, Karl E. Anderson, Gang Jia, Marianne T. Sweetser, Bruce Wang · 发表于：Orphanet Journal of Rare Diseases · 年份：2024 · DOI：10.1186/s13023-024-03284-w · 被引用次数：13 · 研究领域：Porphyrin Metabolism and Disorders、Heme Oxygenase-1 and Carbon Monoxide、Folate and B Vitamins Research

BACKGROUND: Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18-65 years who completed part C of the Phase 1 givosiran study (NCT2452372). METHODS: Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint. RESULTS: Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not...