ARCT-032 well tolerated in CF trial with early positive signs
Trial data show safety and mucus clearance in cystic fibrosis patients
ARCT-032, Arcturus Therapeutics’ experimental inhaled therapy for cystic fibrosis (CF), has been well tolerated so far in a clinical trial. Early imaging data also suggest it may help clear mucus from the lungs, according to interim results announced by the company.
“These findings suggest that ARCT-032 may be addressing the underlying pathology [disease processes] of cystic fibrosis in a meaningful way,” Harm Tiddens, MD, PhD, professor emeritus at Erasmus Medical Center in the Netherlands, said in a press release from Arcturus.
The Phase 2 clinical trial, called LunairCF (NCT06747858), is testing various doses of ARCT-032 inhaled daily for about a month, mainly to evaluate safety. The new data come from six patients given a dose of 10 mg/day.
When these patients started on ARCT-032, some experienced side effects that were reported in an earlier Phase 1 study, which tested single doses of ARCT-032. However, these side effects generally went away over continued treatment, Arcturus reported. The study’s only serious safety issue occurred after dosing ended and was judged unlikely to be related to ARCT-032.
Since safety data from this cohort were largely positive, a monitoring committee authorized the trial to enroll a new cohort of up to six patients who will be given a higher dose, 15 mg/day. The Phase 2 study is recruiting participants at sites in the U.S. It is open to adults with CF who are not eligible for or are not taking CFTR modulators due to drug intolerance, poor response, or lack of access.
Therapy works to normalize CF mucus production
CF is caused by mutations in the gene that encodes CFTR, a protein that helps control mucus production. In CF, lack of functional CFTR leads to the production of thick, sticky mucus that builds up in the lungs and other organs. Medications called CFTR modulators are designed to increase the functionality of the defective CFTR protein in people with certain mutations, but not everyone can benefit. For example, the six people in the Phase 2 trial all had class 1 mutations — meaning they produced no CFTR protein at all — making modulator therapies ineffective for them.
When genes are read to make protein, the genetic code is copied from DNA into messenger RNA (mRNA) — a temporary molecule that’s used as a blueprint for protein production. ARCT-032 is designed to deliver mRNA encoding healthy CFTR to cells in the lungs. This allows the cells to make healthy CFTR protein, which may help normalize mucus production.
The new interim data suggest the therapy may be working as intended. Imaging showed reductions in mucus plugging in four of the six people after a month of ARCT-032 treatment.
“We are particularly encouraged by the early signals of mucus plug reduction in Class I CF participants treated with ARCT-032 because Class I CF individuals do not produce CFTR and therefore do not respond to available CFTR modulator therapy,” said Juergen Froehlich, MD, chief medical officer of Arcturus.
Lung function, measured by forced expiratory volume in one second (FEV1) — the amount of air a person can blow out in a forceful breath — showed no meaningful improvement over the month of the study, Arcturus reported. However, in exploratory analyses that included data collected about two weeks after dosing ended, four people had trends toward increasing FEV1. Arcturus noted the changes fall within the range of variability for this type of lung function measurement.
Overall, these data “warrant further investigation at higher doses and longer treatment durations,” Froehlich said. Arcturus is already prepping for a new clinical trial to test ARCT-032 given for about three months in up to 20 people with CF. The company said it hopes to launch the new trial in the first half of 2026.
“We look forward to initiating our 12-week study in the first half of next year for this promising therapeutic intended to address significant unmet medical need,” Froehlich said.
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