Drug-digital dual therapy for depression starts phase 2
Dr Rebecca Price, associate professor of psychiatry at the University of Pittsburgh School of Medicine, will oversee the trial
An experimental antidepressant in development at Gate Neurosciences has started a proof-of-concept study to see if its efficacy can be boosted by a digital neurocognitive training tool.
The study – which will be run in collaboration with the University of Pittsburgh – will test Gate's apimostinel, a selective modulator of the NMDA receptor, with the digital therapeutic (DTx) invented by Pittsburgh associate Professor of Psychiatry, Psychology and Clinical and Translational Science, Dr Rebecca Price.
The team behind the study hope to show that using the Automated Self-Association Training (ASAT) tool will extend the duration of the antidepressant effect from a single dose of apimostinel, which is being developed as a rapid-acting treatment for major depressive disorder (MDD).
Apimostinel has a similar mode of action to ketamine and derivatives like Johnson & Johnson's Spravato (esketamine) – approved by the FDA for treatment-resistant depression in 2019 and for MDD patients at risk of suicide earlier this year – but is thought to lack some of the psychoactive effects of these drugs.
It's an intravenously administered follow-up to zelquistinel – Gate's lead programme – which is being developed as a once weekly oral treatment for MDD and is in a phase 2 trial.
ASAT is a cognitive behavioural therapy (CBT) programme that uses cognitive tasks to condition patients to associate thoughts about themselves with positive attributes. The new study will test a hypothesis that dosing with apimostinel will prime the brain to be more receptive to the effects of DTx and deliver "a more targeted and efficient method to extend relief in depressed patients."
Dr Price has previously run a study combining ASAT with ketamine, which showed that a single infusion of the drug followed by four days of digital training generated a statistically significant improvement in depression symptoms that lasted for three months.
Typically, the effect of ketamine tends to wear off within seven days and Spravato – currently the only FDA-approved NMDA receptor antagonist for depression - is administered as a nasal spray twice-weekly dose for four weeks. Meanwhile, in a prior single-dose phase 2 study, apimostinel demonstrated rapid and statistically significant antidepressant effects that lasted for up to seven days.
"ASAT was crafted to complement rapid-acting treatments for psychiatric disorders," said Dr Price.
"It is designed to be as efficient as possible with short digital administrations and shows promise for extending single-dose outcomes by months."
Indianapolis-based Gate was founded in 2019 and emerged from stealth in 2022. It has licensed zelquistinel, apimostinel, and related NMDA receptor modulator rapastinel from AbbVie.
Originally developed by Naurex, rapastinel reached phase 3 development at Allergan before it was acquired by AbbVie, but failed in phase 3 development for MDD.
