Vanda puts VQW-765 on hold after Phase III social anxiety miss

Vanda shares fell 6.2% in after-hours trading on Wednesday after the company announced the Phase III failure, Investing.com reported. The VQW-765 programme is on hold pending further analysis of the full dataset, Vanda said.

Study 3201 (NCT07221578) randomized 546 adults aged 18 to 65 at about 30 US sites, one-to-one to a single oral dose of VQW-765 or placebo. All had a current diagnosis of social anxiety disorder and elevated baseline scores on the Liebowitz Social Anxiety Scale and the Public Speaking Anxiety Scale, Vanda said. Participants then took the Trier Social Stress Test, preparing and delivering an interview-style presentation to a panel that gave no feedback or encouragement. The test induces acute stress by design.

The primary endpoint was distress during the performance phase in female participants, rated on the Subjective Units of Distress Scale from 0 to 100, with higher scores meaning more distress. Women on VQW-765 scored 65.6 against 66.0 on placebo. The least squares mean difference was -0.4, with a 95% confidence interval of -5.32 to 4.62 and a p-value of 0.8899. The key secondary endpoint covered the full male and female population. It also missed: 64.7 on the drug against 63.8 on placebo, a difference of 0.9, with a 95% confidence interval of -3.00 to 4.73 and a p-value of 0.6605. Both intervals included zero, so the trial could not separate the drug from placebo.

Study 3201 was designed to confirm Vanda's earlier Phase II trial, Study 2201. In that trial, participants with a history of performance anxiety reported numerically lower stress levels on the drug than on placebo during the TSST. The Phase III result did not confirm those findings. Vanda said VQW-765 was safe and well tolerated, consistent with prior studies.

Mihael H. Polymeropoulos, Vanda's president, CEO and chairman, said: "We are disappointed that Study 3201 did not confirm the earlier Phase II findings for VQW-765 in patients with social anxiety disorder."

Why social anxiety is hard to treat

Vanda estimates that more than 20% of the US population experiences debilitating performance anxiety, from public speaking to test taking, writer's block and musical performance. Public speaking anxiety is the most common form, it says. The figure is an estimate, not a diagnosis count. The trial's enrollment criterion was a current diagnosis of social anxiety disorder. There is no FDA-approved drug treatment for performance anxiety, and general anti-anxiolytic drugs tend to be sedating, Vanda said.

Most available therapies for social anxiety disorder target serotonin or norepinephrine reuptake, and progress in getting new drugs to market has been slow. Neuphoria, formerly Bionomics, scrapped BNC210 in social anxiety disorder last October after a Phase III failure; the drug remains in trials for post-traumatic stress disorder. Vistagen's fasedienol nasal spray recently showed positive results in the open-label extension of the PALISADE-4 study. Jefferies analysts had named Vanda's social anxiety readout a key upcoming catalyst for the company.

The molecule's route to Vanda

VQW-765 is an oral small molecule alpha-7 nicotinic acetylcholine receptor partial agonist, formerly known as AQW-051. Vanda licensed it from Novartis in 2014, when the Swiss company had it in mid-stage trials for schizophrenia. The receptor is a pentameric assembly of alpha-7 subunits. Nicotine can bind the same receptor, but Vanda says VQW-765 binds it with much higher affinity.

What happens next

The programme is on hold pending further analysis of the full dataset. Vanda is not currently exploring VQW-765 in any other indication, according to its website.