New hope for Prader-Willi hunger as Phase 3 trial expands
HERO study seeking participants to test Aardvark’s therapy for hyperphagia
A Phase 3 trial testing the ability of Aardvark Therapeutics’ oral treatment candidate ARD-101 to ease hyperphagia, or insatiable hunger, in people with Prader-Willi syndrome (PWS) is still seeking adolescent and adult participants in the U.S., with other sites planned globally.
Called HERO (NCT06828861), the study is expected to enroll up to 90 people with PWS, 13 years and older, across nine countries. It is currently active in the U.S., and there are planned sites in Canada, Australia, Europe, and South Korea. Top-line data are expected in early 2026.
Details for the trial were described in a recent blog post from the Foundation for Prader-Willi Research and an accompanying webinar that featured Aardvark executives.
“Based on success in … previous trials … we have this potentially pivotal Phase 3 study which we believe moves our drug closer to a potential approval in [PWS],” Tien Lee, MD, Aardvark’s CEO, said in the webinar. Pivotal trials are those meant to produce results that, if positive, will support an application for a therapy’s approval.
Help with study enrollment available
Those interested in participating can find trial locations and get help with enrollment on the study’s website. Aardvark has partnered with a concierge service called Leapcure to connect families to the study.
A hallmark symptom of PWS is hyperphagia, or excessive and uncontrollable hunger. This puts patients with the complex genetic disorder at an increased risk of obesity, diabetes, and other health complications.
ARD-101 is a small molecule designed to bind to and activate bitter taste receptor proteins, which enable the detection of bitter-tasting substances, in the gut. This stimulates the release of two gut hormones, called cholecystokinin (CCK) and glucagon-like peptide-1, that communicate with the brain to control hunger and food intake.
People with PWS reportedly have abnormal regulation of hunger-blocking hormones, including CCK, which may contribute to hyperphagia.
By stimulating the production of these gut hormones and activating this gut-brain signaling, ARD-101 is expected to help regulate hunger for people with PWS without causing toxic side effects in other parts of the body.
Beyond dampening hunger, the gut-brain signaling induced by ARD-101 is expected to have other benefits, like easing anxiety, reducing inflammation and body fat, and preventing constipation, according to Lee.
A previous Phase 2 trial (NCT05153434), based in the U.S. and launched in 2022, evaluated the safety and efficacy of ARD-101 in 18 people with PWS, ages 17 to 65. All participants received oral ARD-101, taken twice daily for about a month, with the dose increasing each week.
Earlier this year, Aardvark reported ARD-101 was well tolerated and led to meaningful reductions in hyperphagia, as assessed by the caregiver-completed Hyperphagia Questionnaire for Clinical Trials (HQ-CT), among trial participants.
Specifically, the treatment led to an average reduction of more than eight points, and up to 16 points, in HQ-CT scores, representing a reduction in hyperphagia. Of 12 participants, 11 exhibited hyperphagia reductions and four achieved near-complete symptom relief, according to the blog post.
Lee noted the findings were “very encouraging … given the degree of change that we saw and how consistent it was.”
Data also showed ARD-101 was associated with a 1.5% reduction in body fat and a 2% increase in lean muscle, in addition to anti-inflammatory and possible anti-anxiety benefits.
Most side effects were mild and temporary. Risks to the liver, kidneys, and immune system are not expected with ARD-101.
This promising data prompted the launch of the HERO trial. All participants must have a primary caregiver that can commit to trial requirements, and during the trial, they cannot use Vykat XR (diazoxide choline), which is the only approved therapy for PWS-related hyperphagia.
Trial participants receive treatment for 12 weeks
Participants are being randomly assigned to receive ARD-101 or a placebo for 12 weeks (about three months). The dose, taken twice daily, will be 200 mg for one week, 400 mg for the next, and then 800 mg for the remaining 10 weeks.
The study’s main goal is to evaluate whether ARD-101 reduces hyperphagia relative to the placebo, as assessed by changes in HQ-CT scores. Researchers will also look “at a number of other secondary [measures], which we have high confidence that we will have a good probability to see benefit” with the experimental therapy, Lee said.
HERO was designed with patient and family convenience in mind, Manasi Jaiman, MD, Aardvark’s chief medical officer, said in the webinar.
“We only actually have four in-person clinic visits and … three telehealth visits built in between those in-clinic visits,” Jaiman said, adding that travel expenses and lodging for the participant and caregiver will be covered. Participants will also be able to maintain their usual diet.
Those completing HERO will have the option to enter an open-label extension study, in which all will receive ARD-101. The plan is for that study to continue until ARD-101 receives regulatory approval.
In addition to PWS-related hyperphagia, Aardvark is developing ARD-101 for a form of obesity caused by damage to a brain region called the hypothalamus.
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