Aardvark Therapeutics has paused the Phase 3 HERO trial and OLE, and the Phase 2 POWER and STRENGTH trials after reversible cardiac QRS prolongation was observed in a healthy volunteer safety study. The company is reviewing the findings with the FDA and expects to provide guidance in Q2 2026.
Written By: Vikas Londhe,
Chief Editor and Patient Safety Expert
Aardvark Therapeutics has voluntarily paused multiple clinical programs evaluating its investigational gut–brain pathway therapy ARD-101 after cardiac conduction changes were observed in a healthy volunteer safety study.
The company had earlier announced in March 2026 a voluntary pause of the Phase 3 HERO trial after reversible cardiac conduction changes were observed in a healthy volunteer safety study.
The current pause includes the Phase 3 Hunger Elimination or Reduction Objective (HERO) trial and its open-label extension (OLE) evaluating ARD-101 for the treatment of hyperphagia in individuals with Prader-Willi syndrome (PWS). Aardvark has also suspended the ARD-201 obesity program, including the Phase 2 POWER and STRENGTH trials, while it evaluates next steps for the broader platform.
Aardvark expects to provide updated guidance on its development programs in the second quarter of 2026.
Cardiac observations triggered precautionary pause
The voluntary pause followed findings from a healthy volunteer cardiac safety study conducted to support anticipated regulatory requirements for a future new drug application.
In the study, two of eight participants experienced QRS duration increases greater than 25% from baseline, while another participant experienced an increase of less than 25%. These changes were observed at a 1,600 mg twice-daily dose, which is twice the target dose used in the HERO trial and was administered without prior dose escalation.
The cardiac findings were not classified as serious adverse events, were not associated with cardiac symptoms, and were reversible after treatment discontinuation without medical intervention.
In a subsequent healthy volunteer cohort receiving 800 mg twice daily, one participant experienced a transient QRS increase greater than 25%, and another experienced a smaller increase. Similar to the earlier observations, these events were reversible and not accompanied by symptoms.
Preliminary analyses suggest a clear exposure–response relationship, where higher plasma concentrations are associated with increased risk of QRS prolongation. Modeling suggests that lower doses such as 200 mg twice daily produce exposures well below the threshold associated with QRS changes.
No cardiac safety signals were observed in previous Phase 1 or Phase 2 trials, and preclinical studies did not predict cardiac liabilities.
Company working with FDA on development strategy
Aardvark is conducting a comprehensive evaluation of the safety data and engaging with the FDA to determine the best path forward.
“Patient safety will always be our highest priority, and we are actively engaging with the FDA with urgency to determine the best path forward for our programs,” said Tien Lee, M.D., Founder and Chief Executive Officer of Aardvark Therapeutics.
Lee noted that despite the pause, the company continues to believe in the therapeutic potential of ARD-101.
“With positive clinical data, an encouraging safety profile from previous trials and our recently developed understanding of the exposure-response relationship with reversible cardiac QRS prolongation, we have confidence in ARD-101,” Lee said. “We strongly believe that ARD-101 retains its potential as a differentiated therapeutic option for hyperphagia in individuals living with PWS.”
The company hopes to resume the PWS development program once regulatory discussions are completed.
Obesity program also temporarily halted
While the safety review is ongoing, Aardvark has also paused the ARD-201 obesity program, which combines ARD-101 with a DPP-4 inhibitor.
The pause affects two Phase 2 studies:
- POWER (Prevention of Weight Regain) – evaluating ARD-201 in patients who lost approximately 15% body weight using GLP-1 receptor agonists
- STRENGTH – evaluating placebo-adjusted weight loss and additive effects of ARD-201 combined with GLP-1 therapy, exercise, and nutrition interventions
Financial runway extends into 2027
Aardvark reported $110 million in cash, cash equivalents, and short-term investments as of December 31, 2025, which the company expects will fund operations into the second quarter of 2027.
The company expects to provide further updates on its development programs in the second quarter of 2026.
References
Aardvark Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business Updates, 23 March 2026, https://ir.aardvarktherapeutics.com/news-releases/news-release-details/aardvark-therapeutics-reports-fourth-quarter-and-full-year-2025
Phase 3 Setback for Aardvark’s ARD-101 as HERO Enrollment Freezes, 03 March 2026, https://pharmacally.com/phase-3-setback-for-aardvarks-ard-101-as-hero-enrollment-freezes/
Vikas Londhe is the Chief Editor and a subject matter expert in patient safety and drug safety. He has a deep understanding of pharmacology, medication-related risks, patient and drug-related errors, and global drug regulatory frameworks. Through his work, he focuses on translating complex medical and regulatory information into clear, evidence-based insights that support safer medication use and informed healthcare decisions.
