Phase 1 Results for Givosiran Published in “The New England Journal of Medicine”

Phase 1 Results for Givosiran Published in “The New England Journal of Medicine”

We published results from the Phase 1 study of givosiran, our investigational RNAi therapeutic for the treatment of acute hepatic porphyria (AHP), in The New England Journal of Medicine (NEJM) in a paper titled “Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria.”

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Read the paper in The New England Journal of Medicine

In the Phase 1 study, the proportion of patients reporting adverse events (AEs) was similar across treatment groups with no clear relationship with givosiran dose. The majority of AEs were mild or moderate; the most common AEs included nasopharyngitis, abdominal pain, and diarrhea. Serious AEs (SAEs) were reported in six patients treated with givosiran (N=33), including – as previously reported – one fatal SAE of hemorrhagic pancreatitis, assessed as unlikely related to study drug by the study investigator. Additional unrelated SAEs included influenza infection, opioid bowel dysfunction, miscarriage, and two patients with abdominal pain. No SAEs were reported in the placebo group (N=10).

Monthly givosiran administration resulted in sustained reductions of ALAS1 mRNA, urinary aminolevulinic acid (ALA), and porphobilinogen (PBG) to near normal levels. In exploratory analyses, these reductions were associated with a 79% decrease in mean annualized attack rate and an 83% decrease in mean annualized hemin usage, compared with placebo.

We are pleased to expand Alnylam’s contribution to the medical literature with the publication of these results in NEJM, and are grateful to the patients and caregivers who participated in the givosiran Phase 1 study. We look forward to the upcoming readout of topline results from the ENVISION Phase 3 trial and, if positive, completing regulatory filings with the goal of quickly bringing givosiran to this underserved patient population.


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