Arcturus Therapeutics Faces Setback in Cystic Fibrosis mRNA Therapy Trial

Arcturus Therapeutics, a San Diego-based biopharmaceutical company, has encountered a significant obstacle in its pursuit of an innovative mRNA therapy for cystic fibrosis (CF). The company's stock plummeted by 55% following the release of disappointing interim data from its phase 2 trial of ARCT-032, an inhaled mRNA treatment for CF patients with Class I mutations.

Efficacy Concerns Emerge in Phase 2 Trial

The open-label, multiple ascending dose phase 2 trial involved six adults with Class I CF who received daily 10 mg doses of ARCT-032 for 28 days. The primary endpoint of the study was to assess the incidence and severity of adverse events. However, investors were particularly focused on the secondary endpoint: changes in forced expiratory volume in one second (FEV1).

Arcturus reported that the initial analysis comparing FEV1 values from the first day to Day 28 failed to show any meaningful improvement. This outcome fell short of the company's previously established benchmark of a 3% increase in FEV1, raising concerns about the therapy's potential to deliver sustained benefits in lung function.

Despite the setback in FEV1 measurements, Arcturus highlighted some potentially promising findings. The company reported reductions in mucus burden for four of the six patients, which some analysts view as an encouraging sign of biological activity.

Safety Profile and Future Plans

Arcturus emphasized that ARCT-032 demonstrated a generally safe and well-tolerated profile during the trial. Treatment-related adverse events observed in an earlier single-dose phase 1 trial were also noted in some participants for the initial few doses but reportedly ceased with continued dosing.

The company is pressing forward with its development program, currently conducting a third stage of the trial that includes six participants receiving higher 15 mg doses. Arcturus has announced plans to launch a 12-week safety and preliminary efficacy study in up to 20 patients in the first half of next year.

Dr. Juergen Froehlich, Chief Medical Officer at Arcturus, expressed optimism about the early signals of mucus plug reduction, particularly given that Class I CF patients do not produce cystic fibrosis transmembrane conductance regulator (CFTR) and therefore do not respond to available CFTR therapies.

As the pharmaceutical industry continues to watch Arcturus's progress, analysts will be keenly observing whether longer treatment duration or higher dosing can improve efficacy signals beyond mucus clearance and reduce data variability in future studies.