Arcturus Begins Phase 2 Dosing for CF and OTC Deficiency Studies

Arcturus Therapeutics Holdings Inc., a San Diego-based company specializing in messenger RNA medicines, has made significant strides in its Phase 2 clinical trials targeting cystic fibrosis (CF) and ornithine transcarbamylase (OTC) deficiency. As of December 2024, the company has initiated dosing for participants in these studies, aiming to explore the efficacy and safety of its investigational mRNA therapeutics.

The Phase 2 trial for cystic fibrosis involves the administration of ARCT-032. Participants will receive daily doses over a 28-day period. This study is crucial as ARCT-032 is designed to address the pressing need for new treatments among CF patients who do not respond to existing therapies. Dr. Pad Chivukula, Arcturus' Chief Scientific Officer, emphasized the potential of ARCT-032 to meet the significant unmet medical requirements of the CF community, particularly for those who are unable to benefit from current treatment options.

Cystic fibrosis is a genetic disorder known for its life-shortening impact, characterized by mutations in the CFTR gene. These mutations hinder the function of CFTR protein in the airways, causing blockages that can lead to infections and progressive lung damage. Despite the availability of CFTR modulators, about 15% of CF patients either lack the necessary CFTR protein or cannot tolerate these drugs. Arcturus is focusing on this group of patients with its ARCT-032, which is an inhaled mRNA therapeutic designed to express functional CFTR in the lungs. This treatment aims to restore CFTR activity, potentially improving patients' respiratory health. The drug has received special designations from both the European Medicines Agency and the U.S. FDA due to its promise in treating this challenging condition.

In tandem with the CF study, Arcturus is progressing with its Phase 2 trial for OTC deficiency using ARCT-810. In December 2024, the first U.S. participant with OTC deficiency began receiving doses of 0.5 mg/kg of ARCT-810. Each participant will undergo five intravenous infusions over a two-month timeframe. This study follows an earlier placebo-controlled trial in Europe and marks an expansion into an open-label study in the United States.

OTC deficiency, a prevalent urea cycle disorder, results from mutations that impair the OTC enzyme in the liver. This enzyme is critical for converting ammonia to urea, and its deficiency can lead to high ammonia levels, which may cause severe neurological issues if untreated. Traditional management options for OTC deficiency include a low-protein diet and nitrogen scavenging medications, which do not address the root cause. ARCT-810 is being developed to enable liver cells to produce the functional OTC enzyme, potentially eliminating the risk of metabolic crises associated with the disorder. The investigational drug has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the FDA, highlighting its potential significance.

Arcturus Therapeutics, established in 2013, continues to leverage its proprietary LUNAR® delivery technology and mRNA expertise to develop treatments for rare diseases like CF and OTC deficiency. The company's efforts in mRNA therapeutics also extend to global collaborations in vaccine development and a joint venture in Japan focusing on mRNA vaccine production. With a strong patent portfolio, Arcturus is well-positioned to advance its pipeline, which includes RNA therapeutic candidates and partnered vaccine programs for various infectious diseases.