Aardvark Pauses Phase 3 ARD-101 Trial for Prader-Willi Syndrome Due to Cardiac Safety Concerns

Aardvark Therapeutics has announced a voluntary pause of its Phase 3 HERO trial, which investigates the efficacy and safety of ARD-101 for reducing hyperphagia in patients with Prader-Willi Syndrome. This decision was prompted by reversible cardiac observations identified during routine safety monitoring in a healthy volunteer study at above target therapeutic doses.

The company is conducting a comprehensive data review and has halted ongoing enrollment and dosing in the trial as a precaution. Aardvark is collaborating closely with the FDA and experts in the Prader-Willi Syndrome community while seeking optimal therapeutic dosing for ARD-101.

Consequently, the company no longer expects to announce topline data from the HERO trial by the third quarter of 2026 and will provide further updates in the second quarter of this year. According to a company statement, enrollment in HERO had been progressing steadily prior to the pause.

The Phase 3 HERO trial is testing ARD-101 in as many as 90 children and adults with PWS-related hyperphagia. In addition to the U.S., participants are being enrolled at sites in Australia, Canada, South Korea, and the U.K. The minimum age in all countries outside the U.S. is 13, except in Australia, where patients as young as 10 are being enrolled.

Prior to the pause, the trial had lowered the minimum enrollment age in the U.S. to allow children as young as 7 to take part. This protocol change was agreed upon by the U.S. Food and Drug Administration's Institutional Review Board, and followed an eligibility expansion last year that reduced the minimum age of trial participants in the U.S. from 13 to 10 years.

HERO participants are being randomly assigned to take either ARD-101 or a placebo twice daily for about three months. For those on the therapy, the dosage increases from 200 mg in the first week to 400 mg in the second week, and to 800 mg thereafter. The study's main goal is to assess changes in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT), a widely used measure of food-seeking behaviors in PWS.

ARD-101 is an oral small molecule that activates gut-based bitter taste receptor proteins to stimulate hormones that tell the brain the body is full. By mimicking this natural signal, the experimental therapy aims to lower appetite and help patients manage the urge to constantly seek out food.

The medication has received orphan drug and rare pediatric disease designations for PWS in the U.S. These statuses are meant to help incentivize and accelerate the development and regulatory review of drugs meant to treat rare conditions, defined in the U.S. as those affecting fewer than 200,000 people.

In a Phase 1 clinical trial involving healthy adults, ARD-101 showed a favorable safety profile. Data from a Phase 2 study enrolling adolescents and adults with PWS showed that about a month of ARD-101 treatment led to meaningful reductions in hyperphagia and favorable changes in body composition, including reduced body fat and increased lean muscle, according to the company.

Participants who complete the trial may enter a long-term open-label extension study, where all will receive ARD-101 for up to a year.