Long-Term Givosiran Effective for Acute Hepatic Porphyria

Among patients with acute hepatic porphyria (AHP) and recurrent attacks, long-term use of givosiran is associated with a decreased annualized attack rate and improved QOL, according to a study in the Journal of Hepatology.

Researchers reported the final 36-month results from the phase 3 ENVISION study (ClinicalTrials.gov Identifier: NCT03338816). Participants were aged 12 years and older with a documented diagnosis of AHP, confirmed AHP genetic mutation or biochemical and clinical criteria consistent with AHP, and 2 or more porphyria attacks within 6 months before enrollment.

The efficacy assessments included annualized attack rate (AAR) of composite porphyria attacks, annualized days of hemin use, proportion of attack-free and hemin-free patients at 3-month intervals, and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG).

The continuous givosiran group included patients who received givosiran from the beginning of the double-blind period and during the open-label extension (OLE). The placebo crossover group comprised patients who had placebo in the double-blind period and givosiran during the OLE (months 7-36). The all-givosiran group included all patients who received givosiran in the double-blind period or the OLE.

The double-blind period included 94 patients (median age, 37.5 years; women, 89%), and the OLE period included 93 patients (47 in the continuous givosiran group and 46 in the placebo crossover group).

The continuous givosiran group had a median AAR of 1.0 in the 6-month double-blind period and a median of 0.4 in the OLE. For the placebo crossover group, the median AAR was reduced from 10.7 in the double-blind period to 0.9 in the OLE. Among all patients, the median AAR was 0.4 during givosiran treatment.

At months 3 to 6, 67% of participants in the continuous givosiran group were attack-free, and 86% were attack-free at months 33 to 36. Among the placebo crossover group, 24% of participants were attack-free at months 3 to 6, and 92% were attack-free at months 33 to 36.

Continuous givosiran treatment was associated with a continual decrease in use of hemin. The median annualized days of hemin use was low in the continuous givosiran group (0 to 0.4) and was reduced by 97% in the placebo crossover group (16.2 to 0.4) from the double-blind period to the OLE period.

The 12-item Short Form Health Survey physical component summary (PCS) scores in the continuous givosiran group improved by 5.1 and 8.6 points, and mental component summary (MCS) scores improved by 3.6 and 8.1 points from baseline to months 6 and 36, respectively. PCS scores improved by 1.7 and 9.4 points and MCS scores improved by 0.4 and 3.2 points for participants in the placebo crossover group.

Continuous givosiran treatment resulted in reduced median urinary ALA and PBG levels.

Adverse events (AEs) occurred in 97% (91/94) of participants, and 37% of patients reported severe AEs. Injection-site reactions (39%) and nausea (37%) were the most common AEs. Serious AEs (SAEs) occurred in 39% of participants.

Study limitations include a relatively small number of patients.

“Patients receiving long-term monthly treatment with givosiran reported improved patient QOL assessment scores, including assessments of physical functioning, activities of daily living, and overall health status,” study authors wrote.

Disclosure: This study was supported by Alnylam Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Gastroenterology Advisor