FDA clears Phase 2 trial of ARCT-032, inhaled mRNA therapy for CF
ARCT-032 has potential to treat all CF patients, regardless of mutation
The U.S. Food and Drug Administration (FDA) has cleared a Phase 2 clinical trial testing ARCT-032, an inhaled therapy candidate, in people with cystic fibrosis (CF).
Arcturus Therapeutics, the therapy’s developer, did not announce when the trial is expected to start.
“The study is designed to evaluate the safety and effectiveness of ARCT-032 administered for several weeks at multiple dose levels in people with CF who do not qualify for, or benefit from, CFTR modulator therapy,” Juergen Froehlich, MD, Arcturus’ chief medical officer, said in a company press release.
CFTR modulators have become standard CF treatment, but not all patients are eligible and some are intolerant to these therapies.
CF is caused by mutations in the CFTR gene, which encodes a protein of the same name that’s essential for producing watery mucus in the airways and other organs. When the protein is faulty or missing, thick and sticky mucus builds up to cause respiratory problems and other disease symptoms.
ARCT-032 delivers healthy copies of CFTR mRNA to cells in lungs
ARCT-032, also known as LUNAR-CF, uses aerosolized, fat-like particles to deliver healthy copies of CFTR messenger RNA (mRNA) directly to cells in the lungs by inhalation, allowing them to produce a functional version of the protein. mRNA is an intermediary molecule that carries genetic instructions from the gene to the protein-producing cell machinery.
The therapy is inhaled using a nebulizer and has the potential to treat all patients, regardless of the CF-causing mutation they carry.
In a ferret model of CF, ARCT-032 was found to increase CFTR protein activity. The treatment was efficiently delivered to the animals’ airways, where it improved mucus clearance.
ARCT-032 was recently shown to be safe in healthy adults taking part in a Phase 1/1b trial (NCT05712538), with reported adverse events being mostly mild, including elevated temperature with headache, back and muscle pain, and nausea.
Seven CF patients, most of whom were on CFTR modulators, were then enrolled. Preliminary data indicated a trend toward better lung function in four patients treated with two doses of ARCT-032. No serious or fever-like side effects have been reported in the patients.
Phase 2 trial to identify safe, effective dose for further testing in CF patients
The now-approved Phase 2 study seeks to identify a safe and effective dose for further testing in people with CF.
“The Phase 2 Study May Proceed notification allows us to investigate ARCT-032 as a potential treatment for CF patients and provides the opportunity to further validate our LUNAR technology to deliver mRNA via inhalation,” Froehlich said.
ARCT-032 has been given rare pediatric disease and orphan drug designations by the FDA, and was named an orphan drug in the European Union. These designations are meant to support and accelerate the development of treatments for rare diseases.
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