FDA Grants Rare Pediatric Disease Designation for Aardvark’s Treatment for Prader-Willi Syndrome

Rare Daily Staff

The U.S. Food and Drug Administration granted Aardvark Therapeutics a Rare Pediatric Disease designation in Prader-Willi Syndrome for its lead program ARD-101 for the treatment of Prader-Willi syndrome, a rare genetic disease characterized by extreme and unabating hunger.

Prader-Willi syndrome (PWS) is a severe neurodevelopmental disorder with a prevalence of about 1 in 15,000-20,000 births. The disorder is caused by the loss of function of several genes located on chromosome 15. PWS impacts multiple organ systems and is characterized by metabolic, endocrine, and neurological dysfunction. One of the hallmark characteristics of PWS is morbid obesity in early childhood, accompanied by developmental delays and musculoskeletal malformations. Obesity in PWS is driven by hyperphagia and mitigated by strict control of food intake. Strict food control, if anything, exacerbates hyperphagia, anxiety and aggressive food-seeking behavior, which is most stressful for those afflicted as well as their caregivers.

Aardvark’s lead product, ARD-101, is a first-in-class oral composition that has shown promising activity in reducing hunger cravings in clinical studies and promoting weight loss in pre-clinical studies. ARD-101 is substantially gut-restricted and has minimal systemic exposure. It is postulated that ARD-101 conveys its systemic effects by activating secretion of several gut peptide hormones, including glucagon-like peptides-1 and -2(GLP-1, GLP-2), and cholecystokinin (CCK). Gut CCK is considered a “satiety signal” that acts via the gut-brain axis to control hunger. PWS patients have a normal CCK receptor but their CCK release from gut enteroendocrine I-cells in response to food is impaired, leaving PWS patients with a continuous sense of extreme hunger. Phase 1 studies demonstrated safety and tolerability in healthy human volunteers. Three phase 2 studies have demonstrated an impact on hunger suppression.

Previously, Aardvark had enrolled 12 subjects in a phase 2 study of oral ARD-101 in PWS led by Diane Stafford at Stanford Children’s Health and Shawn McCandless at Colorado Children’s Hospital. Based on promising results, Aardvark is enrolling additional subjects and exploring higher drug doses.

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases which affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If a Biologics Licensing Application for ARD-101 for the treatment of PWS is approved by the FDA, Aardvark may be eligible to receive a Priority Review Voucher (PRV) that can be redeemed to receive a priority review for any subsequent marketing application or may be sold or transferred. Most recently, Sarepta Therapeutics sold a PRV for $102 million.