An Aardvark Therapeutics clinical trial that has been on voluntary pause for nearly three months due to a safety signal is now formally under an FDA clinical hold, and the biotech said it will unblind the data so far to figure out if its lead metabolic disorder drug candidate has a future.
The full FDA clinical hold announced after Thursday’s market close covers all studies for ARD-101, an Aardvark drug in development for Prader-Willi syndrome. This rare inherited metabolic disorder leads to hyperphagia, or excessive hunger that remains unsatisfied no matter how much a person eats. The resulting morbid childhood obesity leads to respiratory and cardiovascular complications and raises the risk of rupture of the digestive tract.
Aardvark had advanced its Prader-Willi drug to Phase 3 testing. In February, Aardvark disclosed a cardiac safety signal emerged during routine safety monitoring in a healthy volunteer study. The company voluntarily paused enrollment and dosing in the Phase 3 trial while it investigated the heart problem. But the data remained blinded.
As of Feb. 27, when Aardvark announced the voluntary trial pause, 68 patients were dosed in the Phase 3 study and 19 in the open-label extension study. Aardvark now plans to unblind data from both studies. By assessing the drug’s efficacy and safety in study participants, the company said it aims to make an informed decision on the next steps for the program.
Aardvark is proceeding under a tight time table. As of the end of the first quarter of this year, the company reported its cash position was $91.2 million, which it projects will last into mid-2027. But Aardvark will need to find answers about ARD-101 well before then so it can meet with the FDA and resolve the hold. Investors will want to see regulatory certainty before pumping more money into the company for another pivotal study. To William Blair analyst Andy Hsieh, the unblinding of ARD-101’s data could have a silver lining.
“We believe this could provide a path forward by allowing early signals of efficacy to be detected, which would better position Aardvark to design and conduct the second registration-enabling study,” he said in a Friday research note. “We expect a more fulsome update—specifically, a path forward that is aligned with the FDA — later this year.”
ARD-101 is an oral small molecule designed to activate bitter taste receptors, or TAS2 receptors, sparking secretion of gut-peptide hormones that suppress hunger. The twice-daily pill is specifically designed to hit TAS2 receptors in the gut, avoiding these receptors elsewhere in the body where activating them can lead to toxic effects.
Aardvark makes a distinction between hunger, which is discomfort from not having eaten, and appetite, which is a reward-seeking desire for food. The company says hunger and appetite are governed by separate neural signaling pathways and its hunger-suppressing drugs could complement appetite suppression reported in tests of other medicines, such as GLP-1 receptor agonists.
Aardvark took its metabolic disease strategy to the public markets last year with a $94 million IPO. The company is part of a small group of companies conducting research in Prader-Willi, an indication that has seen many clinical trial failures.
The lone Prader-Willi treatment available is Vykat XR, a Soleno Therapeutics drug that won FDA approval last year. Vykat is an oral small molecule formulated as a once-daily pill. It’s thought to work by activating potassium channels that play a role in regulating physiological processes, including appetite. Vykat will continue its commercialization journey as part of Neurocrine Biosciences, which last month announced a $2.9 billion deal to acquire Soleno.
Photo: Streeter Lecka, Getty Images
