Long-term Treatment Shows Sustained Benefit in Patients With Acute Hepatic Porphyria

Long-term givosiran significantly benefits patients with acute hepatic porphyria and repeated attacks by reducing attack frequency, hemin use, and severity of daily worst pain, according to a study published in Liver International.

“Givosiran treatment was also associated with improvement in assessments of physical functioning and quality of life,” researchers wrote.

Supported by Alnylam Pharmaceuticals, the study was a 24-month interim analysis of the ongoing phase 3 ENVISION trial. During a 6-month, double-blind period involving a total 94 patients with acute hepatic porphyria with recurrent attacks, 48 patients received givosiran (2.5 mg/kg monthly) and 46 patients received placebo.

Afterward, 93 patients entered a 30-month open-label extension period: 47 patients continued givosiran (2.5 mg or 1.25 mg/kg monthly) and 46 who had received placebo crossed over to givosiran.

According to 24-month data, patients receiving continuous givosiran had a median annualized attack rate reduction from 1.0 in the double-blind period to .0 in the open-label extension. Patients who crossed over from placebo had a median annualized attack rate decrease from 10.7 to 1.4.

Median annualized days of hemin use were .0 during both the double-blind and open-label periods for continuous givosiran patients and decreased from 14.98 to .71 for crossover patients.

Furthermore, long-term givosiran sustainably lowered delta-aminolevulinic acid and porphobilinogen. The medication improved daily worst pain and patient-reported assessments of quality of life, and had an acceptable safety profile.

“Results demonstrated a trend toward greater reductions in annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, and hemin use in placebo crossover patients treated with givosiran 2.5 mg/kg once monthly, compared with those treated with givosiran 1.25 mg/kg once monthly,” researchers reported. “Consistent with this observation, approximately half of the patients assigned to the 1.25 mg/kg dosing regimen (including those in the placebo crossover group and the continuous givosiran group) had inadequate disease control and required dose escalation to 2.5 mg/kg.”

Consequently, the recommended givosiran dosing is 2.5 mg/kg once monthly, they advised.

Reference:
Ventura P, Bonkovsky HL, Gouya L, et al. Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study. Liver Int. 2022;42(1):161-172. doi:10.1111/liv.15090