Aardvark Therapeutics (Nasdaq: AARD) announced that the US FDA has placed a full clinical hold on its investigational new drug application for ARD-101, formalizing a voluntary pause the San Diego-based company had previously initiated across its Phase III program in Prader-Willi syndrome.
The Aardvark Therapeutics FDA clinical hold applies to all studies operating under the ARD-101 IND, including the HERO trial (AVK-101-301), a randomized controlled Phase III study evaluating ARD-101 for hyperphagia in patients with Prader-Willi syndrome, and its companion open-label extension (AVK-101-302). As of February 27, 2026, 68 patients had been dosed in the HERO trial and 19 in the open-label extension.
ARD-101 functions as a TAS2R (bitter taste receptor) agonist, targeting the gut to stimulate the release of gut-peptide hormones (like CCK) that reduce hunger. The clinical hold follows a voluntary pause that Aardvark had already initiated, meaning the FDA action converts an internal decision into a formal regulatory constraint. The company said it remains in active discussions with the agency to resolve the hold and determine a path forward for the ARD-101 program.
In parallel with its FDA engagement, Aardvark intends to unblind the HERO OLE trial data accumulated to date across both studies. The stated purpose is to assess the totality of available efficacy and safety information before deciding on next steps. No timeline for the unblinding was disclosed, and the company has not indicated when it expects to share results publicly.
The decision to unblind mid-trial is unusual in biopharmaceutical clinical development and typically signals that the sponsor needs clearer visibility into the benefit-risk profile before committing to a path forward — whether that involves seeking to lift the hold, modifying the protocol, or reassessing the program entirely. Aardvark has not specified what safety signal or concern prompted the voluntary pause that preceded the formal FDA clinical hold.
What ARD-101 is and why it matters in PWS
ARD-101 is an oral small-molecule designed to stimulate the release of gut-peptide hormones through activation of bitter taste receptors — specifically the TAS2R class of receptors expressed on enteroendocrine cells of the gastrointestinal tract. By engaging this gut-restricted pathway, the compound is intended to reduce hunger through downstream satiety signaling rather than through central nervous system mechanisms or systemic hormonal exposure.