Aardvark Therapeutics has halted dosing and enrollment in its Phase 3 HERO trial for ARD-101, an experimental treatment aimed at reducing extreme hunger in patients with Prader-Willi syndrome. The company made the decision after “reversible cardiac observations” were found during a safety review in a separate healthy volunteer study, according to a statement released Friday. These findings occurred at doses higher than those used therapeutically. The pause also affects the open-label extension of the HERO trial. Details about the specific cardiac events have not been disclosed.
Following the announcement, Aardvark’s share price fell sharply, opening Monday at $5.76—a drop of approximately 54% from Friday’s closing price of $12.50.
Stifel analysts commented that this cardiovascular signal was unexpected: “this hasn’t been seen in prior preclinical/clinical studies—and regular safety monitoring of HERO has had no issues.” They noted after speaking with Aardvark management that the company plans to meet with the FDA to discuss next steps and remains "optimistic" about ARD-101's future.
Despite management’s optimism, Stifel expressed reservations: “It’s hard for us to have any confidence here,” noting that since cardiac tissue contains the same taste receptors targeted by ARD-101, there is a plausible link between the drug and these safety signals. The analysts also raised concerns about Aardvark's financial position: “Moreover, with runway into 2027 and unclear timelines, the balance sheet is another important question.” As reported on September 30, 2025, Aardvark held $126.4 million in cash and equivalents.
Analysts from William Blair shared similar views regarding increased clinical risk due to the study pause: “Due to severe disruption of the study pause, we do not believe the ongoing Phase III HERO trial will be fully completed.”
Aardvark has not provided an estimated timeline for resuming HERO but acknowledged that it will likely miss its previously stated goal for a topline data readout in the third quarter.
ARD-101 works by activating certain intestinal taste receptors linked to bitterness perception; this action stimulates gut hormones like GLP-1 involved in regulating hunger. In June 2023 Phase 2 results, most participants saw reduced hyperphagia and improved behavior after four weeks of treatment.
Prader-Willi syndrome is a rare genetic disorder marked primarily by chronic feelings of insatiable hunger leading to obesity and related health issues as well as other behavioral and cognitive challenges.
In addition to ARD-101, Aardvark is developing ARD-201 for weight loss and maintenance; both remain at early stages of research.
