Aardvark Therapeutics had previously voluntarily suspended studies of ARD-101—and a related asset called ARD-201—after detecting anomalous echocardiographic readings in healthy volunteers that could indicate reduced heart efficiency.
The FDA has put a full clinical hold on Aardvark Therapeutics’ lead asset for Prader-Willi syndrome, freezing all ongoing trials of the drug due to cardiac concerns observed in a healthy volunteer trial.
The hold, announced Thursday after market close, applies to the Phase 3 HERO study testing the candidate ARD-101 for the treatment of hyperphagia in patients with Prader-Willi syndrome. Aardvark will also have to suspend a late-stage open-label extension of HERO. The biotech is working with the FDA to figure out a way forward for ARD-101.
“It’s hard for us to have any confidence here,” Stifel wrote in a March 1 note to investors, referring to the ARD-101 cardiac observations.
Aardvark crashed nearly 30% to $4.73 per share before the opening bell on Friday.
Even before the FDA’s formal hold, Aardvark in late February paused both HERO and the extension study after detecting “reversible cardiac observations.” These signals arose in a separate healthy volunteer study when participants were dosed at above therapeutic levels.
A few weeks later, these cardiac worries spilled over to Aardvark’s other asset ARD-201, the design and mechanism of which are based on ARD-101. In mid-March, the biotech paused the Phase 2 POWER and STRENGTH studies testing ARD-201 as an obesity treatment. The former is looking at how well the asset could maintain weight loss in patients who had received GLP-1s, while the latter is assessing ARD-201’s additive benefits when used alongside GLP-1s.
According to Aardvark’s analysis, an echocardiograph reading of two patients showed patterns that could be indicative of lower heart efficiency. These patients were given 1,600-mg doses of ARD-101 twice-daily—two times the target dose in HERO.
The biotech conducted heightened dosing in healthy volunteers as part of a routine safety study to support a regulatory application for ARD-101.
The signal “seems plausibly drug-related which we think raises important questions,” the Stifel analysts wrote in the March note. In particular, even if lower doses of ARD-101 prove safe, that could then compromise or cap the drug’s efficacy.
“This adds significant uncertainty and it’s very hard to build confidence in what the path forward may look like,” Stifel said at the time.
The overhang hasn’t yet lifted for Aardvark, with William Blair continuing to harbor concerns for ARD-101 in a May 5 note. “We believe the clinical risk of ARD-101 is elevated,” the analysts wrote. “The cardiac events could be mechanism-based and call into question the therapeutic window of ARD-101.”
In a Q1 report last week, the biotech said that it is still in discussions with the FDA over ARD-101’s future.
