PTC Therapeutics has ceased the development of utreloxastat following the failure of its Phase 2 CardinALS trial in patients with amyotrophic lateral sclerosis (ALS). The global, placebo-controlled study did not meet its primary endpoint of slowing disease progression, as measured by the composite ALSFRS-R and mortality analysis.
While the trial showed a modest numerical benefit on the primary endpoint and a correlation between favorable clinical effect and lowering plasma neurofilament light chain (NfL), a biomarker of neuronal damage, statistical significance was not achieved (p=0.52). Secondary efficacy endpoints also failed to reach significance.
Trial Details and Results
The CardinALS trial (NCT05349721) assessed the efficacy of utreloxastat in slowing the progression of ALS, a rare and fatal neurodegenerative disease affecting motor neurons in the brain and spinal cord. Despite utreloxastat's demonstrated safety and tolerability, the absence of significant efficacy and biomarker signal led to the decision to discontinue its development.
Matthew Klein, CEO of PTC Therapeutics, expressed disappointment, stating, "We are of course disappointed that we were not able to demonstrate treatment efficacy and provide a potential therapy that could address the significant unmet medical need of ALS patients."
Analyst Perspective
William Blair analysts noted that the CardinALS trial results were disappointing but did not significantly impact their investment thesis. They maintain an Outperform rating on PTC, emphasizing the potential approval and launch of sepiapterin for treating Phenylketonuria (PKU) as a key growth driver. A PDUFA decision for sepiapterin is expected in July.
Focus on Other Programs
Analysts also highlight growing investor interest in PTC's Huntington's disease program. Positive discussions with regulators regarding an accelerated approval pathway for PTC-518, a small-molecule therapy, could significantly boost the stock. A Type C meeting with the FDA is planned for the fourth quarter to discuss the regulatory pathway.
Additionally, PTC aims to file a U.S. marketing application for vatiquinone in Friedreich's ataxia (FA) by late 2024. Approval is anticipated based on the drug's clinical data and recent FDA neurology approvals, particularly given the lack of existing treatments for pediatric FA patients.
Sale of Priority Review Voucher
Following the Phase 2 failure, PTC Therapeutics sold its Rare Pediatric Disease Priority Review Voucher for $150 million. The voucher was granted upon FDA approval of Kebilidi (eladocagene exuparvovec-tneq), a gene therapy for children and adults with Aromatic L-amino acid decarboxylase (AADC) deficiency.
