PTC Discontinues ALS Asset Utreloxastat Following Mid-Stage Setback, Analysts Shift Focus to Potential in PKU

PTC Discontinues ALS Asset Utreloxastat Following Mid-Stage Setback, Analysts Shift Focus to Potential in PKU

PTC Discontinues ALS Asset Utreloxastat Following Mid-Stage Setback, Analysts Shift Focus to Potential in PKU

On Tuesday, PTC Therapeutics disclosed that its monitored drug candidate, utreloxastat, did not succeed in the Phase II CardinALS trial aimed at amyotrophic lateral sclerosis (ALS), forcing the New Jersey-based biotech to discontinue this asset.

Details concerning specific outcomes were sparse in the announcement, with PTC stating that utreloxastat failed to meaningfully slow disease progression compared to placebo. This assessment was based on a composite analysis that observed survival at the 24-week mark and assessed functional performance utilizing the ALS Functional Rating Scale-Revised (ALSFRS-R).

Utreloxastat fell short of its secondary goals as well, which included alterations in ALSFRS-R scores, slow vital capacity, sniff nasal inspiratory pressure, and survival rates. Furthermore, the drug was also unable to achieve a significant reduction in plasma levels of neurofilament light chain, a indicator of neuronal impairment.

Due to these unsatisfactory efficacy results, PTC will halt further development of utreloxastat.

Utreloxastat acts as a small molecule inhibitor of 15-lipoxygenase, a potential mechanism intended to decrease oxidative stress and thereby mitigate ALS progression. Additionally, the compound supports the retention of glutathione, an antioxidant whose reduction has been associated with ALS. PTC released first-in-human data for utreloxastat in December 2022, highlighting its safety and tolerability in healthy individuals alongside a favorable pharmacokinetic profile unaffected by gender or dosing timing.

In communication with investors, William Blair analysts labeled the CardinALS results as “unfortunate,” yet they suggested that the Phase II setback would have minimal consequences for PTC’s overall business strategy. “The program was never a focal point in our investment thesis,” they noted, suggesting that the program’s discontinuation would not affect their assessment of PTC.

Instead, the analysts emphasized PTC’s sepiapterin, which they believe “will be a major factor influencing stock performance over the next year.” PTC is advancing sepiapterin for the treatment of phenylketonuria (PKU), a rare genetic condition that impairs the metabolism of phenylalanine. Patients who do not adhere to specific dietary regimens risk facing severe disabilities, including delayed development, seizures, and memory issues.

In May 2023, PTC reported robust Phase III results for sepiapterin in both adult and pediatric PKU patients, demonstrating an average 63% reduction in phenylalanine levels.

William Blair analysts assert that “sepiapterin’s potential in PKU is presently underestimated by the market, with its PDUFA date anticipated for July.” Their note on Tuesday reaffirmed an Outperform rating for PTC.