After cardiac safety signals led to a full clinical hold on Aardvark Therapeutics’ studies of ARD-101, the biotech conducted an additional safety study, in which no cardiac events were detected. Aardvark plans to resume testing the candidate next year.
The FDA has lifted its clinical hold on Aardvark Therapeutics’ small-molecule drug candidate ARD-101, being developed for the treatment of extreme, insatiable hunger in Prader-Willi syndrome, after a new study in healthy volunteers revealed no cardiac events.
Aardvark voluntarily suspended the Phase 3 HERO and open-label extension (OLE) studies of ARD-101 in February, pointing to “reversible cardiac observations.” These signals were detected during a routine safety check in a healthy volunteer study, and occurred in participants who were given the investigational therapy at above-therapeutic doses.
With the regulatory pause removed, Aardvark plans to resume testing ARD-101 in Prader-Willi syndrome (PWS), the biotech said in a Thursday announcement.
“The Company plans to request a meeting with the FDA to align on Phase 3 plans for ARD-101 and expects to resume PWS clinical activities in 2027,” a company spokesperson confirmed to BioSpace over email, but did not provide specific details about the late-stage program.
Patients who were treated with a 1,600-mg dose of ARD-101 twice-daily with no prior dose escalation—two times the strength of the drug in HERO—demonstrated echocardiographic abnormalities that could be indicative of compromised heart efficiency, the company disclosed in its full-year 2025 report in March. Aardvark ran the healthy-volunteer study as part of a “routine additional cardiac safety” assessment to support a planned regulatory filing, the biotech noted.
The FDA placed HERO and the OLE study under a full clinical hold in May. In August, Aardvark said it had unblinded both studies and no longer plans “resume these trials as previously designed.”
Aardvark subsequently ran a “thorough” ECG study in additional healthy volunteers, which revealed no cardiac events when ARD-101 was dosed at 200 mg and 400 mg twice-a-day, according to the Thursday announcement. The biotech also conducted an in vitro cardiac sodium channel (NaV1.5) study.
ARD-101’s suspension has had wide-ranging consequences for Aardvark. In March, shortly after the initial announcement of the voluntary hold, the company also paused the Phase 2 POWER and STRENGTH studies of ARD-201, an asset that combines ARD-101 with a DPP-4 inhibitor and is being tested for obesity.
POWER was designed to test the ability of ARD-201 to help patients keep weight off after GLP-1 treatment, while STRENGTH assessed the additive benefit of ARD-201 when given alongside GLP-1s. Both continue to be listed on Aardvark’s website. The spokesperson declined to provide comments on ARD-201’s current status.
In the wake of these trial pauses, the biotech laid off employees. From 40 employees and 35 consultants at the end of April, Aardvark’s team had shrunk to 28 employees and 27 consultants by July 31. The workforce reduction was revealed in August.
As of June 30, Aardvark had $73.9 million in cash, cash equivalents and short-term investments. The biotech expects this money to “be sufficient to fund operations through the meeting with the FDA to align on Phase 3 plans,” according to the spokesperson.
PWS is a rare and genetic disorder characterized by hyperphagia—the inability to feel full or satisfied, driving a strong urge to keep on eating. Patients with PWS suffer from obesity and related diseases. ARD-101 is designed to activate certain taste receptors in the intestine, especially those that mediate bitterness. This targeting profile leads to the secretion of gut hormones, including GLP-1, to help suppress hunger.
In March 2025, the FDA approved Neurocrine Biosciences’ Vykat XR for the treatment of hyperphagia in PWS. The drug was originally developed by Soleno Therapeutics, which was acquired by Neurocrine for $2.9 billion in April. But it hasn’t been smooth sailing for Neurocrine. A group of doctors in August flagged seven deaths in patients who had taken Vykat XR. Neurocrine is working with the FDA, patient groups and prescribers for a post-marketing surveillance program for patients taking the drug, a spokesperson told BioSpace at the time.
