Trial testing ARD-101 for hunger in PWS to also enroll younger children
HERO study's initial target was 90 Prader-Willi patients ages 13 and older
Aardvark Therapeutics plans to expand its ongoing Phase 3 clinical trial of ARD-101, an oral therapy for easing excessive hunger in Prader-Willi syndrome (PWS), to include patients younger than 13.
The decision, supported by the PWS community, is based on historical data indicating that younger PWS patients are more likely to benefit from treatment, according to a company press release.
The Phase 3 trial, dubbed HERO (NCT06828861), is now testing how well ARD-101 eases hyperphagia — the excessive hunger that is a PWS hallmark — compared with a placebo in as many as 90 teenagers and adults with PWS. Nearly a dozen trial locations are open in the U.S., with other locations planned both in the country and globally.
“Aardvark has made significant progress across our pipeline, and we are well-positioned to unlock the full potential of ARD-101 and ARD-201 [a therapy candidate for obesity] across multiple studies in the year ahead,” said Tien Lee, MD, Aardvark’s founder and CEO.
The company had said it expected top-line data from HERO in early 2026, but now has pushed back that timeframe to between July and September of next year.
Very young children with PWS may have difficulty gaining weight. However, as PWS patients grow older, they develop hyperphagia, leading to excess weight and triggering challenging behaviors, such as anger when seeking food or frustration when it is not available.
ARD-101 is a small, orally available molecule designed to activate bitter taste receptor proteins in the gut. This, in turn, is expected to trigger the release of two hormones that signal satiety, or feelings of fullness, in the brain. By acting largely through the gut, the therapy is expected to help control appetite and related behaviors with minimal side effects in other parts of the body.
ARD-101 may have benefits beyond easing hyperphagia, per developer
After Phase 1 testing showed ARD-101 was safe and well tolerated in healthy adults, the company tested its experimental treatment in 18 adolescents and adults with PWS in a now-completed Phase 2 trial (NCT05153434).
Among the participants, 13 received a fixed ARD-101 dose of 200 mg twice daily for 28 days, or about a month, while the other six were given the medication at an escalating dose. Specifically, these participants received 400 mg twice daily for one week, 600 mg for the next, and 800 mg over the rest of the month. Altogether, 18 patients completed treatment.
At the study’s end, caregivers reported meaningful reductions in hyperghagia, reflected by an average 8.5-point drop on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score.
The results also showed encouraging trends in body composition, with participants experiencing about a 1.5% decrease in body fat along with a more than 2% increase in lean muscle. While the trial was small, these data suggest that ARD-101 may have benefits beyond reducing hyperphagia alone, according to Aadvark.
To build on these data, the ongoing HERO trial is testing ARD-101 against a placebo in a larger number of PWS patients.
Participants are randomly assigned to receive either ARD-101 or a placebo for 12 weeks, or about three months. ARD-101 treatment will be given at a dose of 200 mg twice daily for one week, 400 mg twice daily for the next, and 800 mg twice daily for the remaining 10 weeks, per the developer.
Expansion of the Phase 3 HERO trial to include younger patients below the age of 13 would allow us to reach a larger segment of the PWS patient population through our registration label at launch and serve more patients in need.
HERO’s main goal is to measure changes in HQ-CT scores over the course of the 12 weeks, after which patients will have the option to continue in an open-label extension study, in which all will take ARD-101.
“Expansion of the Phase 3 HERO trial to include younger patients below the age of 13 would allow us to reach a larger segment of the PWS patient population through our registration label at launch and serve more patients in need,” Lee said.
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