Safety concerns over PWS therapy ARD-101 pause global clinical trial
Findings in study involving healthy volunteers halts HERO trial in patients
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Aardvark Therapeutics is voluntarily pausing a global clinical trial testing whether its ARD-101 treatment candidate is superior to a placebo at easing hyperphagia, or insatiable hunger, in people with Prader-Willi syndrome (PWS).
The company’s decision to pause the Phase 3 HERO trial (NCT06828861) was based on concerning findings seen during routine safety monitoring in a study that’s testing the therapy in healthy volunteers. The developer didn’t offer many specifics, but said there were “reversible cardiac [heart-related] observations” at ARD-101 doses above the therapeutic dose that’s being tested in HERO.
Out of an abundance of caution, Aardvark is halting enrollment and dosing in HERO and its open-label extension study (NCT07197034) while these safety data are analyzed.
“The safety of every patient in our clinical studies is our highest priority, so we will thoroughly evaluate the signals seen at higher than therapeutic doses of ARD-101 in a healthy volunteer study,” Tien Lee, MD, founder and CEO of Aardvark, said in a company press release. “We are committed to advancing the ARD-101 clinical program and we are evaluating optimal therapeutic dosing levels to support its progress.”
The Phase 3 HERO trial is designed to test ARD-101 against a placebo in approximately 90 people with PWS, ages 7 and older. The main goal is determining if the experimental treatment is better than the placebo at reducing hyperphagia, a hallmark symptom of PWS. The study has been ongoing at sites in the U.S., the U.K., Canada, South Korea, and Australia.
Participants who complete the trial may enter its extension study, where all will receive ARD-101 for up to a year and will be monitored for long-term outcomes.
No timeline given for when studies will resume
Aardvark didn’t provide a timeline for when it expects these studies to resume, saying it will provide another update within the next few months.
“We will continue to collaborate closely with the [U.S. Food and Drug Administration] and scientific and clinical experts, and we greatly appreciate our partnership with the PWS community as we determine next steps for this program,” Lee said.
The company also expects this trial pause to delay the expected timeline for providing top-line data from HERO, which had been anticipated to be released between July and September.
We will continue to collaborate closely with the [U.S. Food and Drug Administration] and scientific and clinical experts, and we greatly appreciate our partnership with the PWS community as we determine next steps for this program.
ARD-101 is an oral therapy designed to activate taste receptor proteins in the gut, triggering the production of hormones normally released when the gut is full. By increasing levels of these hormones, the medication is expected to help alleviate hyperphagia and risky food-seeking behaviors in people with PWS.
The specific receptor proteins targeted by ARD-101, called TAS2Rs, are also produced by heart cells, so there’s at least a theoretical possibility that the experimental therapy could affect heart health.
Still, in a Phase 1 trial of healthy volunteers, the therapy was generally safe and well-tolerated across all tested doses, without clinically significant findings in lab tests, vital signs, heart assessments, and physical examinations, according to Aardvark. Also, more than 99% of the compound remained in the digestive tract and was not absorbed into the bloodstream.
Before HERO, ARD-101 demonstrated promising efficacy results in a Phase 2 clinical trial (NCT05153434), substantially reducing hyperphagia in adolescents and adults with PWS after one month. Aardvark also reported favorable shifts in body composition, with participants losing body fat while gaining lean muscle.
