Despite the “unfortunate” failure, William Blair analysts do not believe that the utreloxastat readout will heavily affect PTC, instead postulating that the upcoming FDA decision on its phenylketonuria candidate sepiapterin will be a stronger driver of the biotech’s stock.
PTC Therapeutics on Tuesday announced that its closely-watched drug candidate utreloxastat failed the Phase II CardinALS trial in amyotrophic lateral sclerosis, forcing the New Jersey biotech to pull the plug on the asset.
PTC did not provide specific data in its news release, revealing only that utreloxastat was unable to significantly slow disease progression versus placebo in patients with amyotrophic lateral sclerosis (ALS), as measured in a composite analysis that looked at survival after 24 weeks and evaluated functional performance using the ALS Functional Rating Scale-Revised (ALSFRS-R) tool.
Utreloxastat also missed its secondary endpoints, including change in ALSFRS-R score, slow vital capacity, sniff nasal inspiratory pressure and survival. PTC further announced that utreloxastat was unable to significantly lower plasma levels of neurofilament light chain levels, a biomarker of neuronal damage.
With these disappointing efficacy data, PTC will no longer push forward with the development of utreloxastat.
Utreloxastat is a small molecule inhibitor of 15-lipoxygenase, a mechanism of action that developers hoped would allow it to lower oxidative stress and in turn slow ALS progression. Utreloxastat also helps maintain levels of the antioxidant glutathione, a reduction in which has been linked to ALS. PTC published first-in-human data for utreloxastat in December 2022, noting that the drug was safe and well-tolerated in in healthy participants, with an encouraging pharmacokinetic profile unaffected by patient gender and timing of dosing.
In a note to investors, William Blair analysts called the CardinALS readout “unfortunate,” however noting that the Phase II fail will ultimately have little effect on PTC’s business. “The program was never a key part of our investment thesis,” the analysts wrote, adding that the firm considers “the discontinuation of the program as having no impact on our rating” of PTC.
Instead, the analysts pointed to PTC’s sepiapterin, which “will be a key driver of stock over the next 12 months.” The biotech is advancing sepiapterin for phenylketonuria (PKU), a rare genetic metabolic disorder that compromises the body’s ability to break down phenylalanine. Patients with PKU who do not receive a special diet suffer from several severe disabilities, such as delayed development, seizures and memory loss.
In May 2023, PTC released strong Phase III data for sepiapterin in adult and pediatric PKU patients, eliciting a 63% average reduction in phenylalanine levels.
William Blair analysts “believe sepiapterin’s opportunity in PKU is currently underappreciated by the Street, with its PDUFA date expected in July,” according to their note on Tuesday. William Blair retained its Outperform rating of PTC.
