Givosiran effective for acute intermittent porphyria (ENVISION)

Référence

Balwani M, Sardh E, Ventura P, et al, for the ENVISION Investigators. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N Engl J Med 2020;382(24):2289-2301.

Sommaire

Givosiran is a drug that targets messenger RNA and prevents synthesis of delta aminolevulinic acid and porphobilinogen, which are central to causing attacks of acute intermittent porphyria. In this trial, 94 patients, 12 years and older, with acute hepatic porphyria were randomized to once-monthly subcutaneous injections with givosiran 2.5 mg/kg or matching placebo. Randomization was stratified by subtype of porphyria, previous use of hemin prophylaxis (which was discontinued during the trial), and high frequency versus low frequency of attacks. Allocation concealment is not mentioned. The mean age of participants was 39 years, 90% were women, approximately 40% were using prophylactic hemin, and participants were evenly split between those with high versus low numbers of attacks per year. Patients were followed up for 6 months, and all patients completed follow-up. Results are only reported for the 89 of 94 patients with the subtype of acute intermittent porphyria: the annualized attack rate was significantly lower in this group (3.2 vs 12.5 attacks per year; P < .001). Presumably because attacks were not normally distributed, the authors also report the median number of attacks, which were similarly reduced (1.0 vs 10.7). The percentage of patients who reported no attacks was also higher in the girovisan group (50% vs 17%; number needed to treat = 3; statistical significance not reported). A variety of secondary measures, such as quality of life and treatment satisfaction, were also improved. Serious adverse events, including worsening chronic kidney disease and elevation of hepatic transaminases levels, were more common in the treatment group (21% vs 9%). Injection site reactions (25% vs 0%) and nausea (27% vs 11%) were also more common in the givosiran group. This Phase 3 trial was funded, designed, analyzed, and written by the pharmaceutical company.