Arcturus Therapeutics' mRNA Therapy for Cystic Fibrosis Shows Mixed Results in Phase II Trial

Arcturus Therapeutics, a San Diego-based biotech company, has released interim data from its ongoing Phase II trial of ARCT-032, an inhaled mRNA therapy for cystic fibrosis (CF). The results, which have been met with mixed reactions from investors and analysts, reveal both challenges and potential promise for the experimental treatment.

Efficacy Signals and Setbacks

The primary efficacy measure, forced expiratory volume in one second (FEV1), showed no meaningful improvement after 28 days of treatment in the six adult patients with Class I CF who received 10 mg daily doses of ARCT-032. This outcome fell short of the company's previously set benchmark of a 3% increase in FEV1, leading to a significant drop in Arcturus' stock price, which plummeted by 55% following the announcement.

Despite the disappointing lung function results, Arcturus highlighted a potentially promising finding: a reduction in mucus burden observed in four out of six patients. This outcome was detected using AI-enhanced high-resolution computed tomography screening, which the company described as an "encouraging" trend indicative of the asset's therapeutic benefit.

Dr. Harm Tiddens, professor emeritus of pediatric pulmonology at Erasmus Medical Center in the Netherlands, commented on the mucus reduction, stating, "Seeing a trend towards a reduction in mucus plugs and volume after only 28 days of treatment suggests biological activity. Mucus plug reduction can be followed with longer-term lung function improvements over multi-month treatment durations."

Safety Profile and Future Plans

ARCT-032 demonstrated a generally safe and well-tolerated profile in the trial. Treatment-related adverse events identified in an earlier single-dose Phase I trial were observed in some participants during the first few doses but ceased with continued dosing.

Arcturus is proceeding with the next stage of the trial, which will involve six participants receiving higher 15 mg doses. The company also plans to launch a 12-week safety and preliminary efficacy study in up to 20 patients in the first half of 2026. This longer-duration trial aims to "substantiate the clinical relevance" of the mucus results and potentially improve efficacy signals beyond mucus clearance.

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

Market Response and Analyst Perspectives

The mixed results have led to a reassessment of ARCT-032's potential by both investors and analysts. William Blair analysts, while noting the "potentially promising" mucus reduction data, have reduced their probability of success for the program from 40% to 25%. They emphasized the need for Arcturus to establish whether longer treatment duration or higher doses of ARCT-032 can boost efficacy signals beyond mucus clearance.

As Arcturus continues to develop ARCT-032, the company faces the challenge of demonstrating clinically meaningful benefits in a field dominated by established therapies such as Vertex Pharmaceuticals' Trikafta and the recently approved Alfytrek. The coming months will be crucial as Arcturus gathers more data and refines its approach to addressing the underlying pathology of cystic fibrosis with its innovative mRNA therapy.