Vanda Pharmaceuticals’ VQW-765 failed to meet both key efficacy endpoints in a Phase 3 social anxiety trial, leaving the program on hold.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Vanda Pharmaceuticals announced on October 14, 2026, that its Phase 3 clinical study of VQW-765, an investigational alpha-7 nicotinic acetylcholine receptor (α7-nAChR) partial agonist, failed to meet its primary endpoint in adults with social anxiety disorder. The findings did not confirm the efficacy signal observed in an earlier Phase 2 trial, prompting the company to place the development program on hold pending further analysis.
Phase 3 Study Fails to Demonstrate Efficacy
The multicentre, randomized, double-blind, placebo-controlled study, VP-VQW-765-3201 (Study 3201; NCT07221578), enrolled 546 adults aged 18–65 years across approximately 30 clinical sites in the United States. Participants had a current diagnosis of social anxiety disorder and elevated baseline scores on the Liebowitz Social Anxiety Scale and Public Speaking Anxiety Scale.
Participants received a single oral dose of VQW-765 or placebo in a 1:1 ratio before undergoing the Trier Social Stress Test (TSST). This standardized psychosocial challenge involves preparing for and delivering an interview-style presentation to a panel that provides no feedback or encouragement.
The primary endpoint measured distress during the performance phase of the TSST among female participants, using the Subjective Units of Distress Scale (SUDS), which ranges from 0 to 100, with higher scores indicating greater distress.
Among women in the intention-to-treat (ITT) population, the least-squares mean SUDS score was 65.6 with VQW-765 (standard error [SE], 1.90) and 66.0 with placebo (SE, 1.96). The least-squares mean difference was −0.4 points (95% confidence interval [CI], −5.32 to 4.62; p=0.8899), showing no statistically significant treatment advantage.
The key secondary endpoint, which assessed performance-phase distress in the combined male and female ITT population, was also not met. Mean scores were 64.7 with VQW-765 (SE, 1.50) and 63.8 with placebo (SE, 1.51). The least-squares mean difference was 0.9 points (95% CI, −3.00 to 4.73; p=0.6605).
Both comparisons failed to demonstrate a statistically significant reduction in distress. The confidence intervals crossed zero, and the numerical difference in the overall population did not favour VQW-765.
Phase 3 Results Do Not Confirm Earlier Phase 2 Findings
Study 3201 was designed to confirm findings from Vanda’s earlier Phase 2 study, VP-VQW-765-2201, which evaluated a single oral dose of VQW-765 in 230 adults with a history of public-speaking anxiety.
In the Phase 2 study, the overall population showed a numerical trend toward lower performance-phase distress with VQW-765, but the difference was not statistically significant (p=0.1443). Female participants showed a statistically significant response (p=0.034). An exposure-response analysis also reported a significant improvement among women in the middle 50% of drug-exposure levels (p=0.005).
The Phase 3 results did not reproduce a statistically significant benefit in the female population or the overall study population. Although the earlier findings provided a rationale for further investigation, the confirmatory results weaken the evidence supporting VQW-765 as an on-demand treatment for acute anxiety associated with social anxiety disorder.
The available Phase 3 announcement does not provide detailed results for additional endpoints or analyses that could explain the difference between the trials. Further assessment will depend on the complete Study 3201 dataset.
Safety Findings and Development Status
Vanda reported that VQW-765 was safe and well tolerated, consistent with prior studies. However, the announcement did not provide detailed adverse-event frequencies or specific safety outcomes, limiting independent assessment of the reported safety findings.
VQW-765, formerly known as AQW-051, is a small-molecule partial agonist targeting the α7 subtype of nicotinic acetylcholine receptors. Novartis licensed the compound to Vanda for potential development in psychiatric disorders.
Following the Phase 3 results, Vanda placed the VQW-765 program on hold pending further analysis of the full dataset. The company has not announced that development has been permanently discontinued.
Clinical Interpretation
The Phase 3 findings do not establish a statistically significant benefit of VQW-765 for reducing acute, performance-related distress in adults with social anxiety disorder. The failure to confirm the earlier Phase 2 signal, including the female subgroup finding, weakens the current efficacy case despite the reported tolerability. Because the study assessed distress during a standardized performance challenge, the results should not be generalized to all symptoms or treatment settings associated with social anxiety disorder. Further development remains uncertain while Vanda evaluates the complete dataset.
References
Vanda Pharmaceuticals Provides Update on VQW-765 Clinical Development Program, Vanda Pharmaceuticals, 14 October 2026
He Y, Polymeropoulos CM, Mohrman MA, et al, Efficacy and safety of an alpha 7-nicotinic acetylcholine receptor agonist, VQW-765, in subjects with performance anxiety: randomised, double-blind, placebo-controlled trial. Br J Psychiatry. 2025 Jul;227(1):473-480, https://doi.org/10.1192/bjp.2025.84
Study to Evaluate the Efficacy and Safety of VQW-765 for the On-Demand Treatment of Social Anxiety Disorder, ClinicalTrials.gov ID NCT07221578
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.