Vanda Puts Social Anxiety Program on Hold After Asset Fails Phase 3 Study

Vanda Pharmaceuticals has suspended development of its experimental social anxiety treatment after a Phase 3 study failed to achieve its primary goal, raising further questions about the prospects for new medicines targeting the disorder.

The trial enrolled 546 adults with social anxiety disorder, randomly assigning them to receive either placebo or a single oral dose of VQW-765. The experimental drug is a small-molecule partial agonist of the alpha-7 nicotinic acetylcholine receptor.

Following administration, participants completed a psychosocial stress assessment designed to simulate an anxiety-provoking social situation. They were asked to prepare and deliver a presentation resembling a job interview to a panel that offered neither encouragement nor feedback.

Among women, distress scores did not improve significantly with VQW-765 compared with placebo, resulting in a failure to meet the primary endpoint. The study also fell short of a secondary endpoint that assessed outcomes across both male and female participants.

Vanda had restricted its main efficacy analysis to women after results from an earlier-stage study indicated that female participants appeared to respond more favorably. In that Phase 2 study, the company reported a statistically significant treatment effect among women, although the overall study population did not demonstrate the same result.

Because the Phase 3 findings did not reproduce that earlier efficacy signal, Vanda has placed the program on hold while it evaluates the complete dataset.

The outcome adds to the difficulties faced by companies attempting to develop new therapies for social anxiety disorder. Vistagen, another biotech pursuing this market, failed to meet its primary endpoint in a Phase 3 study of fasēdienol in December and encountered another late-stage setback in June. Despite those results, the company continued preparing to engage with the U.S. Food and Drug Administration after a post-hoc analysis identified a nominally significant improvement in a subgroup of patients.

VQW-765 has also followed a lengthy development path. Novartis initially investigated the compound as a potential treatment for schizophrenia before transferring its rights to Vanda in 2014. The candidate had already reached Phase 2 development by that point, and Vanda subsequently initiated a Phase 2 study evaluating its potential in anxiety disorders in 2021.

VQW-765 is an investigational small-molecule partial agonist of the alpha-7 nicotinic acetylcholine receptor, being explored for its potential to treat psychiatric conditions. The compound binds to these receptors, which consist of five subunits of the alpha-7 subtype, and increases their activity. Although nicotine also interacts with α7-nAChR, VQW-765 has a substantially greater binding affinity, supporting its potential as a potent, receptor-selective compound. Previously known as AQW-051, the drug candidate was licensed to Vanda Pharmaceuticals by Novartis.

Estimates suggest that more than one in five people in the U.S. experience debilitating performance anxiety. Situations that can trigger this anxiety include public speaking, taking examinations, performing music and experiencing writer’s block. Among these situations, speaking in front of an audience is considered the most common source of performance-related anxiety.