Aardvark Therapeutics Pauses ARD-101 Prader-Willi Syndrome Trials After Cardiac Signal in Healthy Volunteers
Aardvark Therapeutics has voluntarily paused enrollment and dosing in its Phase III HERO trial and open-label extension study evaluating ARD-101 for the treatment of hyperphagia in individuals with Prader-Willi Syndrome, according to a company disclosure issued on March 23, 2026. The ARD-101 clinical trial pause was triggered by unexpected but reversible cardiac observations — specifically, increases in QRS duration — detected in a separate cardiac safety study conducted in healthy volunteers who do not have PWS. The company said it is conducting a comprehensive data review and working with the US FDA to determine next steps, with further guidance expected in the second quarter of 2026.
What the Cardiac Safety Data Show
The cardiac findings that prompted the ARD-101 Phase 3 trial pause emerged from a study Aardvark described as a routine cardiac safety study intended to satisfy anticipated requirements for a future New Drug Application. In the first cohort of eight healthy volunteers dosed at 1,600 mg twice daily — twice the 800 mg twice daily target dose used in the HERO trial — without prior dose escalation, two participants experienced QRS duration increases greater than 25% from baseline, a threshold defined as significant per protocol. One additional participant had a QRS increase of less than 25% from baseline.
A follow-on cohort of 23 healthy volunteers was subsequently dosed at 800 mg twice daily for up to one week, again without dose escalation. In this group, one participant experienced a transient QRS increase of less than 25% from baseline, and one additional participant experienced a QRS increase exceeding 25%. In both cohorts, the company reported that the QRS increases were not classified as serious adverse events, were not accompanied by serious cardiac symptoms, and resolved upon drug discontinuation without medical intervention.
Aardvark stated that preliminary exposure-response analysis indicates a clear relationship between higher plasma concentrations and increased risk of QRS prolongation. Exposure-response modeling suggested that a 200 mg twice daily dose yields plasma concentrations substantially below the threshold where QRS effects were observed. The company noted that no cardiac signals had been detected in prior Phase I or Phase II clinical trials of ARD-101 and that preclinical studies did not predict cardiac safety liabilities.
The HERO Trial and Its Place in the Prader-Willi Syndrome Pipeline
The HERO trial — Hunger Elimination or Reduction Objective — represents the most advanced clinical evaluation of ARD-101 for Prader-Willi Syndrome hyperphagia treatment. The study employed a stepwise dose-escalation approach: 200 mg twice daily for one week, then 400 mg twice daily for one week, followed by 800 mg twice daily for 10 weeks. This contrasts with the healthy volunteer studies, where participants received full doses without prior escalation. The total number of patients enrolled in the HERO trial was not disclosed, nor were any efficacy data reported. The primary endpoint of the trial was not specified in the company's disclosure.
The Prader-Willi Syndrome pipeline update extends beyond the HERO trial. Aardvark also voluntarily paused trials of ARD-201, a fixed-dose combination of ARD-101 and a dipeptidyl peptidase-4 inhibitor being evaluated in two Phase II obesity studies — the POWER trial for prevention of weight regain after GLP-1 receptor agonist therapy and the STRENGTH trial assessing additive effects with GLP-1 receptor agonists.