ARCT-810 (LUNAR-OTC): An Investigational mRNA Therapy for Ornithine Transcarbamylase Deficiency

1. Executive Summary

ARCT-810 is an investigational messenger RNA (mRNA) replacement therapy currently under development by Arcturus Therapeutics. It is designed to address Ornithine Transcarbamylase (OTC) deficiency, a rare and potentially life-threatening X-linked urea cycle disorder. The therapeutic strategy involves intravenous administration of ARCT-810, which utilizes the proprietary LUNAR® lipid nanoparticle (LNP) delivery platform to transport functional OTC mRNA to hepatocytes. This approach aims to enable the patient's own liver cells to synthesize the deficient OTC enzyme, thereby restoring or augmenting urea cycle function and mitigating the toxic accumulation of ammonia.[1]

Preclinical studies in relevant animal models of OTC deficiency provided proof-of-concept, demonstrating successful mRNA delivery, functional enzyme expression, correction of biochemical abnormalities, and improved survival.[4] Phase 1 clinical development involved single ascending dose (SAD) studies in healthy adult volunteers (ARCT-810-01) and subsequently in adult patients with stable, mild OTC deficiency (ARCT-810-02). These studies established an initial safety and tolerability profile, characterized the pharmacokinetics of the mRNA and LNP components, and identified infusion-related reactions (IRRs) as a manageable adverse event.[5]