The FDA lifted its clinical hold on ARD-101 in October 2026, after Aardvark Therapeutics paused its Phase 3 HERO trial over a serious cardiac adverse event. The resolution matters because the hold’s root cause turned out to be a drug-drug interaction rather than an intrinsic property of ARD-101: a serious cardiac event at 800 mg twice daily occurred in a participant also taking pitolisant, a CYP2D6 substrate whose plasma levels rise when co-administered with a CYP2D6 inhibitor. The FDA concurred with that interpretation. ECG studies in healthy volunteers showed no QRS or QT prolongation at 200 mg or 400 mg twice daily, and the agency has agreed Aardvark may run an open-label trial at the 200 mg twice-daily dose in PWS patients.
The exploratory data from the terminated HERO and open-label extension (OLE) trials are limited but directionally consistent. HERO enrolled 67 of a planned 90 participants before early termination, so evaluable patients dropped from roughly 30 per arm at Week 2 to about 11 to 13 per arm by Week 12. Within those constraints, ARD-101 showed numerically greater reductions in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) scores than placebo at Weeks 2, 4, and 8, and patients who crossed from placebo to ARD-101 in the OLE recorded an additional 6-point average drop in HQ-CT score within four weeks. Adverse event rates were similar between arms, with treatment-emergent events in 52% of ARD-101 participants versus 50% on placebo. None of this is conclusive, and Aardvark has been explicit that the efficacy data cannot support reliable interpretation.
The company enters 2027 with $60.3 million in cash, down from $73.9 million at the end of June, which it projects will fund operations through year-end 2027. A meeting with the FDA on the proposed clinical development plan is scheduled for the first quarter of 2027. Vykat XR (diazoxide choline extended-release tablets) is currently the only FDA-approved therapy for hyperphagia in PWS, approved for patients aged 4 and older, so Aardvark is developing ARD-101 for a condition where approved options remain narrow. An estimated 10,000 to 20,000 people in the United States live with PWS, virtually all affected by hyperphagia to some degree.
The practical question that FDA feedback in Q1 2027 will answer is what trial design and dose the agency will accept for a path toward registration. Any plan Aardvark finalizes will need to address CYP2D6 substrate co-medication restrictions, since the interaction with pitolisant and other CYP2D6 substrates that may be used in the PWS population, was central to the safety signal that prompted the hold in the first place.
Source link: https://www.sec.gov/Archives/edgar/data/1774857/000119312526459373/ck0001774857-20261113.htm
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
