Aardvark Therapeutics Initiates International Expansion of Phase 3 HERO Trial for Prader-Willi Syndrome Treatment
Key Insights
Aardvark Therapeutics (search) has dosed the first patient in Australia for its Phase 3 HERO trial evaluating ARD-101 for hyperphagia (search) in Prader-Willi syndrome (search) patients.
The company has received regulatory clearance to enroll patients in Canada and the United Kingdom, with strong US enrollment supporting Q3 2026 topline data readout timeline.
All patients who completed the 12-week trial have enrolled in the Open Label Extension, indicating strong patient engagement and interest in the therapy.
Aardvark Therapeutics (search) has achieved a significant milestone in its Phase 3 HERO trial by dosing the first patient in Australia, marking the international expansion of its pivotal study evaluating ARD-101 for hyperphagia (search) associated with Prader-Willi syndrome (search) (PWS). The company announced that regulatory clearance has also been received for clinical trial sites in Canada and the United Kingdom to begin enrollment.
"We have seen very strong interest in the HERO trial within the patient community, which has been driving enrollment in the United States and in our newly opened Australia sites," said Tien Lee, M.D., Founder and Chief Executive Officer of Aardvark. The robust enrollment across multiple regions continues to support the company's timeline for topline data readout in Q3 2026.
Strong Patient Engagement Signals Treatment Interest
A particularly encouraging development is that all patients who have completed the 12-week clinical trial to date have enrolled in the Open Label Extension trial. "This is an encouraging indicator of patient interest and engagement," noted Dr. Lee. The high retention rate suggests that patients and families are experiencing meaningful benefits from the investigational treatment.
Dr. Manasi Jaiman, Chief Medical Officer of Aardvark, emphasized the critical unmet need in the PWS community: "Significant unmet needs continue to persist in the PWS community, and many families are eager for a therapy that could ameliorate the relentless hunger that is a hallmark of PWS."
HERO Trial Design and Global Expansion
The Hunger Elimination or Reduction Objective (HERO) trial (NCT06828861) is a randomized, double-blind, placebo-controlled Phase 3 study designed to enroll 90 patients across multiple countries including the US, Australia, Canada, the United Kingdom, and South Korea. The primary endpoint measures change in the Hyperphagia (search) Questionnaire for Clinical Trials (HQ-CT) score from baseline to Week 12.
Secondary outcome measures include changes in Caregiver Global Impression of Severity (CaGI-S) for hyperphagia (search) in PWS patients and Clinical Global Impression of Severity (CGI-S) score for hyperphagia in PWS patients. US trial sites are actively enrolling, while Australian sites began enrollment in November. Canadian and UK sites are expected to initiate enrollment shortly following regulatory clearance.
Based on the strong enrollment momentum, Aardvark anticipates it will not need to activate previously planned sites in the European Union to fully enroll the HERO trial and meet its Q3 2026 timeline for topline data readout.
Novel Mechanism of Action Targets Hunger Pathways
ARD-101 represents a novel approach to treating hyperphagia (search) through its mechanism as a gut-restricted small molecule agonist of select taste receptors (TAS2Rs (search)) expressed on the luminal side of the intestine. 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 (search) and the satiety hormone cholecystokinin (CCK).
This mechanism activates gut-brain neurologic signaling to mediate hunger, distinguishing it from appetite-focused therapies. ARD-101 has demonstrated an ability to reduce hunger when used alone or in combination with currently available GLP-1 (search) therapies. The FDA has granted ARD-101 both Orphan Drug Designation and Rare Pediatric Disease Designation for PWS.
Broader Pipeline Development
Beyond the HERO trial, Aardvark is developing ARD-201 (search), a planned fixed-dose combination of ARD-101 with a DPP-4 inhibitor, through two separate Phase 2 trials. This combination approach aims to address some of the limitations of currently marketed GLP-1 (search) therapies for obesity (search) and obesity-related conditions.
The company's focus on hunger suppression represents a distinct approach from traditional appetite-focused treatments. Aardvark defines hunger as "the discomfort from not having eaten recently" and describes it as "a distinct neural signaling pathway separate from appetite, the reward-seeking desire for food."