Verge Genomics has terminated its Phase 1b clinical trial evaluating VRG50635 in patients with amyotrophic lateral sclerosis (ALS), according to an update on ClinicalTrials.gov (NCT06215755). The sponsor cited a lack of supportive risk–benefit data as the reason for discontinuing the study.

The open-label, multiple ascending dose trial was designed to assess the safety, tolerability and pharmacokinetics of VRG50635, a PIKfyve inhibitor identified using Verge’s AI-driven drug discovery platform, in up to 54 adults with sporadic or familial ALS. The study had been active but not recruiting prior to termination.

No safety signals or efficacy data have been publicly disclosed, and the registry update does not specify whether the decision was driven by emerging clinical findings, preclinical reassessment, or broader portfolio prioritization.

VRG50635 previously completed a Phase 1 trial in healthy volunteers, while a Phase 1b/2a was ongoing or planned in ALS patients.

Key takeaways

ALS remains a highly challenging therapeutic area, with a strikingly high clinical trial failure rate. In the last five years, several high-profile drug candidates—including both repurposed and novel agents—have failed in late-stage clinical trials, leading to market withdrawals and program discontinuations. Prior to VRG50635, the most notable recent failures include Amylyx’s Relyvrio (AMX0035), Cytokinetics’ reldesemtiv, and antisense oligonucleotide programs from Biogen/Ionis and Denali/Calico. The high failure rate of ALS clinical trials is attributed to disease heterogeneity, lack of robust biomarkers, and limitations in preclinical models. Recent Emory University research suggests that some drugs reach the CNS but do not affect key disease drivers, emphasizing the need for better biomarkers and mechanistic understanding.