The Food and Drug Administration has approved Givlaari (givosiran; Alnylam) for the treatment of adults with acute hepatic porphyria (AHP).
AHP is a rare, genetic disease characterized by episodic and potentially life-threatening attacks. The disease is comprised of 4 subtypes that result from genetic defects affecting the heme biosynthesis pathway in the liver; this causes the accumulation of neurotoxic heme intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG). Givosiran is a subcutaneously-administered RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1); treatment is expected to lower induced liver ALAS1 levels and decrease these intermediates.
“Prior to today’s approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients.”
The approval of Givlaari was based on data from the ENVISION phase 3 study. The study evaluated the efficacy and safety of givosiran in 94 patients with a documented diagnosis of AHP. Eligible patients were randomized 1:1 to receive once monthly subcutaneous injections of Givlaari or placebo during the 6-month double-blind period. Efficacy was measured by the rate of porphyria attacks that required hospitalizations, urgent healthcare visit, or intravenous hemin administration at home.
Results showed that, on average, AHP patients on Givlaari experienced 70% (95% CI: 60%, 80%) fewer porphyria attacks compared with placebo (mean rate of porphyria attack: 1.9 (95% CI: 1.3, 2.8) with Givlaari vs 6.5 (95% CI: 4.5, 9.3) with placebo; rate ratio: 0.3 (95% CI: 0.2, 0.4); P<.0001). Treatment with Givlaari also resulted in a reduction in hemin use, urinary ALA, and urinary PBG.
With regard to safety, the most common adverse reactions were nausea and injection site reactions. As anaphylaxis has occurred with Givlaari treatment, healthcare professionals should ensure that medical support is available to manage anaphylactic reactions.
Givlaari is expected to be available for shipment to healthcare providers by the end of the year. It is supplied as a ready-to-use solution in single-dose vials (189mg/mL).
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