The US Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation for oral denatonium acetate (ARD-101) to treat Prader-Willi syndrome (PWS), Aardvark Therapeutics announced.

The designation, announced via news release, is accompanied by a phase 2 trial of oral ARD-101 that is now open for additional enrollment of participants.

PWS is a severe genetic disorder affecting neurodevelopment and characterized by extreme hunger (hyperphagia), morbid obesity in childhood, and neurological, metabolic, and endocrine dysfunction. Patients with PWS also experience developmental delays and musculoskeletal malformations. Currently, there is no approved drug to treat the hyperphagia experienced by patients.

ARD-101 is an oral small molecule bitter taste receptor agonist. It acts by increasing the production of peptide hormones in the gut that regulate appetite, such as glucagon-like peptides-1 and -2 and cholecystokinin (CCK). Gut CCK controls hunger by acting as a satiety signal, and patients with PWS have impaired release of CCK.

Read more about PWS therapies

Preclinical studies in animal models of obesity showed that oral use of ARD-101 reduced food intake and body weight. A phase 1 randomized, placebo-controlled trial of single or multiple ascending doses of ARD-101 in healthy adults showed that it had a favorable safety profile and was well tolerated at all doses.

The clinical results indicated that at a dose of 240 mg of ARD-101, circulating gut peptide hormone levels were increased and that treatment was over 99% restricted to the gut with minimal systemic exposure.

The phase 2 trial previously enrolled 12 participants at 2 centers in the United States. With promising results and the new Rare Pediatric Disease Designation, Aardvark Therapeutics is now enrolling additional participants and will assess higher doses of ARD-101.


Aardvark Therapeutics announces receipt of FDA Rare Pediatric Disease Designation for Prader-Willi syndrome and expands the ongoing phase 2 clinical trial. News release. Aardvark Therapeutics, Inc.; August 3, 2023.