Aardvark Expands PWS Trial, Offering Hope to Younger Children

SAN DIEGO, CA – February 10, 2026 – Aardvark Therapeutics has taken a significant step to broaden the reach of its pivotal clinical trial for a new Prader-Willi Syndrome (PWS) therapy, potentially offering hope to a younger and more vulnerable group of patients. The company announced it has received Institutional Review Board (IRB) approval and submitted plans to the FDA to lower the minimum eligibility age for its Phase 3 HERO trial from 10 to 7 years old.

The trial is evaluating ARD-101, a novel drug candidate designed to combat the insatiable, life-altering hunger known as hyperphagia, which is the defining and most challenging symptom of PWS. This protocol amendment could accelerate enrollment and provide crucial data on the benefits of earlier intervention in this rare genetic disorder.

The Unrelenting Challenge of Prader-Willi Syndrome

Prader-Willi Syndrome is a complex and devastating genetic condition affecting approximately 1 in 15,000 people worldwide. Caused by the loss of function of genes on chromosome 15, it impacts metabolism, growth, and cognitive function. While infants with PWS often struggle with poor muscle tone and an inability to feed properly—a stage known as "failure to thrive"—the condition undergoes a dramatic and cruel shift in early childhood.

Between the ages of two and eight, a switch flips, and children develop hyperphagia, an unrelenting and all-consuming drive to eat. This is not simple hunger; it is a constant, torturous sensation of starvation that overrides feelings of fullness. The brain's satiety signals fail, leaving individuals in a perpetual state of food-seeking. This symptom, combined with a slower metabolism, puts patients at extreme risk for rapid weight gain and life-threatening obesity.

For families, managing PWS becomes a 24/7 battle. Caregivers must create a "food-secure" environment, often locking refrigerators and pantries, to prevent dangerous overeating, choking, or even gastric rupture. The behavioral challenges, including temper outbursts and obsessive-compulsive tendencies centered around food, place an immense emotional and physical burden on the entire family. Until recently, treatment has been limited to strict environmental control and growth hormone therapy, which helps with body composition but does not address the underlying hyperphagia.

A Novel Approach Targeting the Gut-Brain Axis

Aardvark Therapeutics' ARD-101 represents a fundamentally different approach. Instead of directly targeting brain chemistry, it works within the digestive system. ARD-101 is a gut-restricted small molecule designed to activate specific bitter taste receptors (TAS2Rs) located on the surface of intestinal cells.

When these receptors are stimulated, they trigger the release of a cascade of natural gut hormones, including cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). These hormones are crucial players in the body's natural hunger and satiety signaling system. CCK, in particular, is known as a key satiety hormone, sending "I'm full" messages to the brain via the gut-brain neurologic pathway. By mimicking this natural process, ARD-101 aims to reduce hunger and restore a sense of fullness that is absent in individuals with PWS.

“We are very pleased to report this important protocol expansion, which allows us to broaden the patient population for our Phase 3 HERO trial to include children as young as 7 years of age in the U.S.,” said Tien Lee, M.D., Founder and Chief Executive Officer of Aardvark. “Hyperphagia may begin early in life for some individuals with PWS, and it presents a persistent burden for patients and caregivers. Expanding eligibility reflects our commitment to addressing the urgent need in the PWS community for a differentiated therapy and we aim to ensure broad and equitable access.”

The FDA has already granted ARD-101 both Orphan Drug Designation and Rare Pediatric Disease Designation, acknowledging its potential to treat a serious condition in a small patient population.

Expanding the Front Lines in a Competitive Field

The landscape for PWS treatments is becoming increasingly active, reflecting a long-overdue focus on this underserved community. In March 2025, Soleno Therapeutics received FDA approval for Vykat XR (diazoxide choline), the first drug specifically indicated for treating hyperphagia in PWS for patients aged four and older. This approval set a new benchmark and validated the pursuit of pharmacological solutions for the condition.

Aardvark is not alone in the race to provide better options. Other companies are exploring different mechanisms, from Rhythm Pharmaceuticals' setmelanotide, which targets the melanocortin-4 receptor (MC4R) pathway, to Tonix Pharmaceuticals' intranasal oxytocin therapy, TNX-2900. Each approach tackles the complex neurobiology of PWS from a different angle.

By lowering the age of eligibility for the HERO trial, Aardvark strategically positions ARD-101 to address the critical window of early childhood when hyperphagia takes root. This move could not only accelerate enrollment in its 90-patient international trial but also differentiate ARD-101 by demonstrating its efficacy and safety in a younger population, a key consideration for physicians and families seeking early intervention.

The Significance of Early Intervention and Trial Design

The decision to include seven- to nine-year-olds in the HERO trial is more than a logistical adjustment; it's rooted in a strong clinical rationale. Intervening before the long-term metabolic and behavioral consequences of unchecked hyperphagia become severe could dramatically alter the disease's trajectory. Capturing data from this younger group will provide a more complete picture of ARD-101's potential impact across a broader spectrum of disease progression.

The Phase 3 HERO (Hunger Elimination or Reduction Objective) trial is a randomized, double-blind, placebo-controlled study—the gold standard in clinical research. The primary goal is to measure the change in hyperphagia from baseline to week 12 using a validated tool, the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Secondary measures will assess the impressions of both caregivers and clinicians on the severity of the condition. Following the 12-week study, all participants will have the option to enroll in an open-label extension, giving them continued access to the drug.

Dr. Lee noted that enrollment is “progressing steadily” and remains on track for a topline data readout in the third quarter of 2026. This upcoming data release is a highly anticipated catalyst for the company and the PWS community, as it will offer the first large-scale glimpse into whether ARD-101's unique gut-focused mechanism can truly make a difference for those living with the constant burden of insatiable hunger. For families with young children just beginning to face the challenges of hyperphagia, this expanded trial represents a tangible step forward.