The U.S. Food and Drug Administration (FDA) has accepted and granted priority review status to Alnylam Pharmaceutical’s new drug application (NDA) seeking approval of givosiran for treating acute hepatic porphyria (AHP).
Priority review means the FDA’s decision on whether to approve the therapy is expected within six months instead of the 10 months under standard review. A decision is expected to be made by Feb. 4, 2020.
Givosiran, also known as ALN-AS1, is an investigational RNA-based therapy (meaning it targets the RNA, a molecule generated from DNA and the template for protein production). The therapy blocks the activity of the aminolevulinic acid synthase 1 (ALAS1) enzyme, preventing the accumulation of toxic molecules that cause AHP.
Anylam’s NDA submission to the FDA was based on data from the company’s Phase 3 ENVISION trial.
The study (NCT03338816) randomized 94 AHP patients, including 89 with acute intermittent porphyria (AIP), to receive givosiran, at a dose of 2.5 mg/kg administered by a subcutaneous (under-the-skin) injection once a month, or a placebo.
Data from an interim analysis of 41 patients showed that treatment with givosiran significantly decreased the levels of aminolevulinic acid (ALA), a key biomarker of AHP, in the patients’ urine, compared with the placebo.
Full updated data from the trial showed that givosiran decreased by 74% the annual rate of porphyria attacks compared to patients treated with a placebo. In addition, it lowered the levels of ALA in the patients’ urine by 92%, which was in agreement with previous results from the interim analysis.
Patients who completed the six-month treatment period in the ENVISION trial (99% of them), decided to continue treatment with givosiran for an additional 30 months in an open-label extension study.
Givosiran was found to be safe and well-tolerated by patients, with no new safety concerns. The most common adverse side effects seen during the trial in givosiran-treated patients included nausea, injection site reactions, abnormal kidney function, and fatigue.
Alnylam has submitted a Marketing Authorization Application (MAA) of givosiran to the European Medicines Agency (EMA), which has also been accepted.
Givosiran received breakthrough therapy designation from the FDA and priority medicines, or PRIME, designation from the European Medicines Agency (EMA), as well as orphan drug status from both regulatory agencies.