ARO-ENaC Study for Cystic Fibrosis Paused Over Safety Concerns


Unfortunately, clinical trials do not always go the way that researchers intend. Sometimes, issues arise during early or preclinical studies which cause enough concern to stop or pause the trials. According to Cystic Fibrosis News Today, this is what recently happened with the Phase 1/2 ARO-ENaC clinical trial. Due to toxicity issues in a separate rat study, drug developer Arrowhead Pharmaceuticals (“Arrowhead”) has voluntarily paused screening, dosing, and enrollment for patients in this clinical trial.


According to Arrowhead, ARO-ENaC is an RNA therapy:

designed to reduce production of the epithelial sodium channel alpha subunit (αENaC) in the airways of the lung. In cystic fibrosis patients, increased ENaC activity contributes to airway dehydration and reduced mucociliary transport.

In short, ENaC overactivity may cause dehydration, lung damage or poor lung function, infection, and more mucus in the lungs. By targeting and inhibiting this channel, ARO-ENaC works to improve lung function and patient outcomes. In the past, ENaC targeting therapies did not offer sustained or durable responses. Additionally, these therapies caused kidney issues. ARO-ENaC has shown to not cause these problems in preclinical studies; in fact, the therapy reduced mucus production in sheep models of CF.

However, an ongoing toxicology study in rat models of CF showed lung inflammation, a potential safety issue. Arrowhead is still collecting toxicology data from a primate study. Though researchers are unclear whether lung inflammation could be a safety issue in the Phase 1/2 AROENaC1001 study, they made the decision to halt the study until further information is known. As explained by Arrowhead CMO Dr. Javier San Martin, MD, patient safety is the top priority. Once more information is known, Arrowhead will inform the public about the decision to continue the clinical trial program.

Cystic Fibrosis (CF)

CFTR gene mutations cause cystic fibrosis (CF), an inherited disorder which causes progressive digestive and respiratory damage. Normally, CFTR regulates salt movement throughout the body. With these mutations, however, patients’ mucus becomes thick and sticky, accumulating throughout the body. Ultimately, this leads to a variety of health issues, ranging from clogged airways and frequent infections to lung damage, respiratory failure, and poor nutrient absorption. Typically, CF is more common in Caucasian newborns than those of other backgrounds. Symptoms associated with CF include:

  • Exercise intolerance
  • Infertility (in males)
  • Shortness of breath and/or difficulty breathing
  • Persistent cough or wheezing
  • Salty skin
  • Constipation
  • Poor weight gain
  • Frequent lung infections
  • Stuffy nose
  • Foul-smelling or greasy stools
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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