Arcturus Therapeutics Faces Setback in Cystic Fibrosis mRNA Therapy Trial

Arcturus Therapeutics, a San Diego-based biopharmaceutical company, has reported disappointing interim results from its phase 2 clinical trial of ARCT-032, an investigational inhaled mRNA therapy for cystic fibrosis (CF). The news, released on October 22, 2025, has led to a significant drop in the company's stock price and raised questions about the therapy's potential efficacy.

Efficacy Concerns in Phase 2 Trial

The ongoing open-label, multiple ascending dose phase 2 trial involved six adults with Class I CF, a form of the disease caused by a protein synthesis defect. Participants received daily 10 mg doses of ARCT-032 via inhalation for 28 days. The trial's primary focus was on safety and tolerability, with efficacy measures as secondary endpoints.

The most notable efficacy measure, forced expiratory volume in one second (FEV1), showed no meaningful improvement when comparing Day 1 to Day 28 values. This falls short of the company's previously set benchmark of a 3% increase in FEV1, which was a key expectation for investors.

Despite the lack of improvement in lung function, Arcturus reported some potentially promising findings. Four out of six patients experienced reductions in mucus burden, which the company views as an encouraging sign of biological activity.

Safety Profile and Future Plans

ARCT-032 demonstrated a generally safe and well-tolerated profile during the trial. Treatment-related adverse events (AEs) observed in an earlier single-dose phase 1 trial were noted in some participants for the initial doses but subsided with continued treatment.

Arcturus is currently conducting a third stage of the trial, administering 15 mg doses to six participants. The company plans to launch a 12-week safety and preliminary efficacy study involving up to 20 patients in the first half of 2026.

Market Reaction and Expert Opinions

The news of ARCT-032's lackluster efficacy results had an immediate impact on Arcturus Therapeutics' stock price, which plummeted by 55% from $23.16 to $10.44 per share by midday following the announcement.

Dr. Juergen Froehlich, Chief Medical Officer at Arcturus, expressed optimism about the early signals of mucus plug reduction, emphasizing the significance for Class I CF patients who do not respond to available CFTR therapies.

Dr. Harm Tiddens, professor emeritus of pediatric pulmonology at Erasmus Medical Center in the Netherlands, suggested that the trend towards mucus plug reduction after just 28 days of treatment indicates biological activity. He noted that such reductions could potentially lead to improved lung function over longer treatment periods.

Analysts at William Blair have reduced their probability of success for the ARCT-032 program from 40% to 25% but remain "somewhat optimistic" about the therapy's potential. They will be closely watching future studies to see if longer treatment duration or higher dosing can improve efficacy signals and reduce data variability.