When Aardvark Therapeutics announced earlier this month that it was pausing a phase 3 trial of its lead metabolic candidate, investors could take solace in the fact that the biotech’s obesity program remained untouched. Those good feelings have now melted away, as Aardvark has elected to put the kibosh on two phase 2 trials of its oral weight loss asset ARD-201.
The paused trials were testing ARD-201’s ability to prevent weight gain and to promote weight loss in combination with a GLP-1 drug and lifestyle changes, Aardvark said in a full-year earnings release March 23. Aardvark announced its intent to run the two trials last August following promising preclinical data.
The pause comes as the San Diego biotech “conducts a comprehensive review of the data” on ARD-201, which is a combination of the gut-targeting taste receptor agonist ARD-101 and a DPP-4 inhibitor.
ARD-101 was the subject of Aardvark’s prior voluntary pause, with its phase 3 trial for the rare genetic disease Prader-Willi syndrome shut down due to “reversible cardiac observations at above target therapeutic doses.”
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ARD-101 is designed to stimulate enteroendocrine cells of the digestive tract to provoke the release of GLP-1 and the satiety hormone cholecystokinin, all with the goal of reducing hunger. Prader-Willi syndrome is marked by hyperphagia, where patients constantly want to eat because they never feel full.
William Blair analysts said in a note this morning that they believed the “clinical risk of ARD-101 is elevated, as the cardiac events could be mechanism-based and call into question the therapeutic window of ARD-101.”
“As a potential silver lining to the phase 3 pause, the occurrence of the cardiac events could allow early unblinding of the study … pending discussions with the FDA,” the analysts added in the March 24 note. “This could provide a path forward by allowing early signals of efficacy to be detected, which would better position Aardvark to design and conduct the second registration-enabling study.”
In a statement yesterday, Aardvark founder and CEO Tien Lee, M.D., said patient safety “will always be our highest priority.”
“We are actively engaging with the FDA with urgency to determine the best path forward for our programs,” Lee added.
As recently as December, William Blair analysts had suggested that ARD-201 could “serve as an oral and more tolerable alternative” to the approved GLP-1 blockbusters from Eli Lilly and Novo Nordisk. The fact that “both the maintenance and induction settings are being investigated offer investors multiple shots on goal,” the analysts noted at the time.
The decision to pause ARD-201’s trials means Aardvark’s entire pipeline is now on hold. News of ARD-101’s temporary halt sent Aardvark’s share price spiraling down by 54% in early March. After initially trading around $16 per share following its $94 million IPO last year, Aardvark’s stock closed trading Monday at $4.06.
