Aardvark Therapeutics has received FDA alignment on a protocol amendment to expand its Phase 3 HERO trial of ARD-101 for treating hyperphagia associated with Prader-Willi Syndrome (PWS), lowering the minimum age of eligibility from 13 to 10 years old. The clinical-stage biopharmaceutical company announced the expansion will enable access to a larger segment of the PWS patient population.
"Expansion of the Phase 3 HERO trial to include children 10 years of age and older will allow us to reach a larger segment of the PWS patient population to potentially serve more patients in need," said Tien Lee, M.D., Founder and Chief Executive Officer of Aardvark. "This decision to expand eligibility is driven by support from the PWS community, alongside historical data showing that younger patients are more likely to benefit from early intervention."
Novel Mechanism Targets Hunger Pathways
ARD-101 represents a novel therapeutic approach as a gut-restricted small molecule agonist of select taste receptors (TAS2Rs) expressed in the intestinal lumen. As a potent bitter taste receptor pan-agonist, ARD-101 stimulates enteroendocrine cells of the digestive tract to release multiple gut-peptide hormones including GLP-1 and the satiety hormone Cholecystokinin (CCK), which activates gut-brain neurologic signaling to mediate hunger.
The compound has demonstrated an ability to reduce hunger when used alone or in combination with currently available GLP-1 therapies. The FDA has granted ARD-101 both Orphan Drug Designation and Rare Pediatric Disease Designation for PWS, recognizing the significant unmet medical need in this rare disease population.
Addressing Insatiable Hunger in PWS
Prader-Willi Syndrome is a rare genetic disorder characterized by insatiable hunger, presenting significant challenges for patients and families. Aardvark's therapeutic approach recognizes that hunger - the discomfort from not having eaten recently - represents a distinct neural signaling pathway separate from appetite, which involves the reward-seeking desirability of food.
The company's development programs explore therapeutic applications in hunger-associated indications and potential complementary uses with anti-appetite therapies. Beyond ARD-101, Aardvark is also developing ARD-201, a fixed-dose combination of ARD-101 with a DPP-4 inhibitor, conducting two separate trials with a goal of addressing limitations of currently marketed GLP-1 therapies for obesity and obesity-related conditions.
Timeline and Clinical Development
The company expects topline data readout from the potentially pivotal Phase 3 HERO trial in the third quarter of 2026. The expanded patient population reflects both community support and clinical evidence suggesting earlier intervention may provide greater therapeutic benefit for PWS patients.
The protocol amendment represents a significant milestone for Aardvark as it advances ARD-101 through late-stage clinical development, potentially positioning the compound to address a critical unmet need in the PWS patient community where treatment options remain limited.
