As reported on BioPharmaDive, Aardvark Therapeutics has halted dosing and enrollment in its late‑stage HERO trial for ARD‑101, a first‑in‑class treatment candidate for Prader–Willi syndrome (PWS), following the discovery of unexpected cardiac findings in a separate study involving healthy volunteers. The pause comes only months before the company had anticipated reporting pivotal Phase 3 results.
According to the company, routine monitoring uncovered reversible electrocardiogram abnormalities in participants who were receiving doses substantially higher than those used in the HERO study. While details remain limited, the observations were significant enough for Aardvark to suspend both the main trial and its open‑label extension while a full safety review is conducted. Updated guidance is expected next quarter.
CEO and founder Tien Lee, MD, stated that patient safety remains central to the company’s decision‑making and emphasized Aardvark’s intention to continue evaluating ARD‑101 while determining the most appropriate dosing strategy. Still, the development injects uncertainty into one of the more advanced therapeutic programs for PWS, a condition historically resistant to drug treatment—particularly for its hallmark symptom of severe, persistent hunger.
The pause also comes at a time of heightened attention on the PWS market. The FDA’s recent approval of Vykat from Soleno Therapeutics marked the first effective treatment for hyperphagia, rapidly propelling Soleno to profitability and signaling strong commercial demand. Yet questions about Vykat’s long‑term outlook and safety profile have left room for potential competitors, a gap Aardvark had hoped ARD‑101 would fill. The company went public in early 2025, raising $94 million to support the drug’s development.
ARD‑101 is designed to activate bitter taste receptors located in the gut, which play roles in appetite control, metabolism, and inflammation. Earlier attempts to target these receptors systemically have raised safety concerns due to their presence in heart and lung tissue. Aardvark has argued its gut‑targeted approach would avoid off‑target effects, an assumption now facing scrutiny.
Analysts reacted cautiously to the announcement. RBC Capital Markets noted that the newly observed heart‑related signals, though reversible, suggest a narrower safety margin than previously assumed. Stifel analysts pointed out that PWS patients already carry elevated cardiovascular risk, complicating regulatory perceptions if cardiac effects are confirmed, even at higher-than-therapeutic doses.
Investor response was swift: Aardvark’s share price dropped by more than half in early Monday trading, while Soleno’s stock saw modest gains.
It remains unclear whether Aardvark will be able to resume the HERO trial as planned or whether further modifications or additional studies will be required. For now, the future of ARD‑101, and its potential role in an evolving therapeutic landscape for Prader–Willi syndrome, hangs on the outcome of the company’s ongoing safety analysis.
