Aardvark Shares Data From Stopped Prader-Willi Trial as FDA Lifts Hold

Aardvark Therapeutics reported exploratory efficacy and safety data on Oct. 23 from its terminated Phase 3 HERO trial and open-label extension of ARD-101, a day after announcing that FDA had lifted the clinical hold on the program.^1,2 The company said the data are directionally consistent but not sufficient to draw definitive conclusions because the trial was stopped early and was not powered to assess efficacy.¹

How did the program get here?

The path to this week's announcements ran through several stages. Aardvark voluntarily paused enrollment and dosing in HERO and the OLE on Feb. 27, 2026, after reversible cardiac observations in a healthy volunteer study.³ FDA placed the ARD-101 program on clinical hold in May and specified human safety studies required to resume clinical work in PWS.³

The company terminated HERO and the OLE in June and said it did not intend to resume them as designed.³ Aardvark then unblinded the data accumulated across both trials to assess the totality of available efficacy and safety information.¹

What do the exploratory data show?

HERO randomized 67 of the 90 planned participants, so all efficacy data are considered exploratory.¹ Aardvark reported:

• A modest reduction in HQ-CT score versus placebo at week two of dose escalation on ARD-101.¹
• After ARD-101 was discontinued, the treatment group's average HQ-CT score returned to near baseline, while the placebo group showed less rebound.¹
• In the OLE, participants who switched from placebo to ARD-101 had an average 6-point reduction in HQ-CT score.¹
• A similar pattern on caregiver and clinician global impression measures.¹

The company said ARD-101 was generally well tolerated, with most adverse events mild to moderate.¹

What was the cardiac safety finding?

One cardiac serious adverse event occurred in HERO at 800 mg twice daily in a participant who was also taking pitolisant, a CYP2D6 substrate.¹ Aardvark said FDA concurred the event was related to a drug-drug interaction.¹

For clinical operations teams, the detail illustrates how concomitant medication use can become the central issue in a trial's safety narrative, and why sponsors and CROs track it closely at the site level. That observation is the editor's context, not a finding from the company's release.

What did it take to lift the hold?

In announcing the hold lift, Aardvark said no cardiac events were observed in a recently completed ECG study at ARD-101 doses of 200 mg and 400 mg twice daily.² The company said it completed the work needed to allow clinical studies to resume.²

What happens next?

Aardvark plans to request an FDA meeting to align on a new Phase 3 design intended to support a future marketing application.¹ The company plans to resume dosing in patients with PWS at a dose lower than the 800 mg twice-daily dose studied in HERO and the OLE, pending FDA discussion, and expects to resume PWS clinical activities in 2027.¹

The company hosted an investor webcast on Oct. 23 to review the data.¹

Sources

1. Aardvark Therapeutics. Aardvark Therapeutics Reports Exploratory Data from the Terminated HERO and Open-Label Extension Trials. GlobeNewswire, Oct. 23, 2026. biospace.com/press-releases/aardvark-therapeutics-reports-exploratory-data-from-the-terminated-hero-and-open-label-extension-trials
2. Aardvark Therapeutics. Aardvark Therapeutics Announces FDA Has Lifted the Clinical Hold on ARD-101 for the Treatment of Prader-Willi Syndrome and Will Host Webcast to Review the Available Exploratory Phase 3 HERO/OLE Data. GlobeNewswire, Oct. 22, 2026 (SEC Form 8-K, Exhibit 99.1). sec.gov/Archives/edgar/data/0001774857/000119312526428943/ck0001774857-ex99_1.htm
3. Aardvark Therapeutics. Form 10-Q for the quarter ended June 30, 2026. SEC. sec.gov/Archives/edgar/data/0001774857/000119312526344987/ck0001774857-20260630.htm