Givosiran Improves Attack Rate, QOL in Patients With Acute Hepatic Porphyria

Researchers assessed the safety and efficacy of long-term treatment with givosiran in patients with acute hepatic porphyria.

The following article is a part of conference coverage from the American College of Gastroenterology 2021 Annual Meeting , held from October 22 to 27, 2021. The team at Gastroenterology Advisor will be reporting on the latest news and research conducted by leading experts in gastroenterology. Check back for more from ACG 2021.


Long-term treatment with givosiran led to sustained and continuous improvements in attack frequency and quality of life (QOL), as well as reductions in hemin use, in patients with acute hepatic porphyria (AHP), according to research presented at the American College of Gastroenterology (ACG) 2021 Annual Meeting, held from October 22 to 27, 2021, in Las Vegas, Nevada and virtually.

The findings were part of the 24-month interim analysis of the ENVISION trial (NCT03338816). Patients with AHP included in the trial (aged ≥12 years) had ≥2 attacks that required hospitalization, urgent care, or at-home intravenous hemin in the 6 months prior to enrollment. The investigators randomly assigned patients to monthly subcutaneous 2.5 mg/kg givosiran (n=48) or placebo (n=46) for up to 6 months. A total of 93 patients later received 2.5 or 1.25 mg/kg givosiran in the open-label extension.

Researchers evaluated and reported the urinary levels of neurotoxic heme intermediates 5-aminolevulinic acid (ALA) and porphobilinogen (PBG) as well as annualized days of hemin use. Additionally, the investigators assessed QOL using the 12-item Short Form Health Survey (SF-12), EuroQOL visual analog scale (EQ-VAS), and Porphyria Patient Experience Questionnaire (PPEQ).

During the open-label extension period, treatment with givosiran in the continuous group was associated with sustained reductions in median urinary ALA and PBG to “near-normal levels,” according to the researchers. In the placebo crossover group, the drug led to a >75% sustained reduction in median urinary ALA and PBG during the open-label extension. Additionally, continued givosiran therapy was associated with a sustained reduction in attacks and hemin use in both the continuous givosiran group and the placebo crossover arm.

Approximately 83% of patients in the continuous givosiran group were “attack-free” per 3-month intervals at months >21 through 24. In addition, 68% of patients in the continuous givosiran group did not require hemin during the open-label extension phase.

The researchers also reported improvements in QOL and activities of daily living during the open-label extension period, as based on the change from baseline in mean SF-12 Physical Component Summary score (continuous givosiran, 8.9; placebo crossover, 10.0) compared with the double-blind period (continuous givosiran, 5.7; placebo crossover, 1.9). Improvements were also observed on the EQ-VAS and PPEQ.

The primary adverse events reported by the researchers were injection-site reactions and increases in serum aminotransferases. A total of 3 patients (3.2%) discontinued therapy due to side effects.

Researchers concluded that this interim analysis “further confirms that long-term givosiran provides sustained and continuous benefit to patients with AHP.”

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

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Bonkovsky HL, Ventura P, Goura L, et al. Efficacy and safety of givosiran in patients with acute hepatic porphyria: 24-month interim analysis of the phase 3 ENVISION randomized clinical trial. Presented at: ACG 2021 Annual Meeting; October 22-27, 2021; Las Vegas, NV and virtual. Abstract P1806.