Renexxion Seeks FDA OK to Test Naronapride for GI Problems in CF
Company planning 1st clinical trials of treatment candidate in CF patients
Renexxion is seeking clearance from the U.S. Food and Drug Administration (FDA) for clinical testing of the treatment candidate naronapride in people with cystic fibrosis (CF) and gastrointestinal (GI) problems.
The Ireland-based biopharmaceutical company, which specializes in treatments for gastrointestinal disorders, announced the opening of an investigational new drug application (IND) with the FDA. It’s seeking approval to evaluate the use of naronapride for CF patients in need of GI-targeted medications.
The oral small molecule already has been tested in humans for a range of GI conditions, but the IND application is “a first step towards conducting clinical trials of this drug candidate in CF patients,” the company stated in a press release.
“We are very excited about the potential of naronapride to improve the quality of lives of individuals with CF,” said Peter Milner MD, chairman and CEO of Renexxion.
“We have received constructive input from the FDA on both our clinical development plan and Phase II clinical trial design. Receiving IND clearance represents a major milestone in moving forward with our clinical development plan,” Milner added.
Testing naronapride for GI problems in CF
Specifically, Renexxion wants to develop naronapride for the treatment of GI dysmotility — impairments to the muscles of the digestive system that lead to problems moving food through the digestive tract.
This condition is accompanied by symptoms such as abdominal pain, nausea, vomiting, bloating, and constipation. People experiencing GI dysmotility also might become malnourished, due to ineffective absorption of nutrients from food.
The hallmark buildup of thick, sticky mucus in CF can affect the digestive tract, leading to difficulties breaking down and absorbing food. As such, gastrointestinal problems are a common symptom in CF, with GI dysmotility affecting more than half of patients.
“The global cystic fibrosis patient community remains in need of effective treatments for gastrointestinal motility complications,” said Zachary Sellers, MD, PhD, assistant professor of pediatrics-gastroenterology at Stanford University School of Medicine, in California.
“Despite advances in treatments for the pulmonary complications of cystic fibrosis, no pro-motility drugs have replaced cisapride since its withdrawal from the market,” Sellers added.
Cisapride was a pro-motility medication that was pulled from the U.S. market in 2000 due to cardiovascular side effects.
Naronapride is a small molecule oral GI “prokinetic,” or a medication intended to enhance GI motility. Its mechanisms are twofold. First, it works to activate 5-HT4 receptors, which stimulate the release of acetylcholine, a chemical that increase gut motility. Second, it inhibits activity at D2 receptors, which normally work to slow gut motility.
It’s also intended to avoid systemic, off-target side effects, including cardiac problems, by being specifically active in the gut.
The experimental treatment has been tested in 11 clinical studies and more than 1,000 people. That includes Phase 2 clinical trials in patients with various GI conditions, such as chronic idiopathic constipation and gastroesophageal reflux disease, known as GERD.
Data have shown, overall, that the treatment is safe, without cardiovascular risks. It also has been shown to be effective for GI indications.
There are no other prokinetics in active development for the CF population, according to Renexxion, which believes will place naronapride as a best-in-class therapy should it eventually be approved.
Miller said the decision to develop naronapride for CF came from discussions with the CF Foundation, CF key opinion leaders, and its European GI licensing partner.
“We welcome clinical trials of naronapride in cystic fibrosis patients with gastrointestinal motility disorders,” said Dhiren Patel, MD, associate professor of pediatrics at the St. Louis University School of Medicine, in Missouri. “If naronapride is proven to be effective in treating these patients, it would significantly improve their quality of life.”