The past month has seen a succession of publications offering support for Click Therapeutics’ digital offering for patients with major depressive disorder (MDD).

The studies, published in npj Digital Medicine, the Journal of Affective Disorders, and presented at the Society of Biological Psychiatry Annual Scientific Convention in New York, showed the therapeutic to reduce symptoms, pair well with transcranial direct-current stimulation (tDCS), and invoke a clear neurobiological mechanism related to cognitive control and emotion processing.

“The data from these studies combined are incredibly encouraging for [Emotional Faces Memory Task (EFMT)] as an effective treatment for MDD,” Brian Iacoviello, director of scientific affairs at Click Therapeutics and an assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai (ISMMS), said in a statement. “Not only do we observe symptom improvement in adults with MDD, and adults with medication resistant depression when combined with tDCS, but for the first time we have shown that EFMT can have the neuroplastic effects expected in key brain regions involved in MDD, and that these changes are associated with symptom improvement.”

In the npj Digital Medicine study, researchers provided 28 patients with MDD 18 sessions with the EFMT intervention, while a separate group of 23 controls received a computerized working memory training program. After the six-week study period, analysis found a significantly greater reduction in MDD symptom severity from baseline among the group receiving the digital therapeutic. Further, 10 of the 28 intervention patients met the predetermined criteria for a clinical response to the treatment, as opposed to four of the 23 controls, and both both groups showed similar minor improvements in their working memory.

“The magnitude of the effect was similar to a previously published pilot study, and the specific symptoms that appear to respond to the intervention are consistent with the hypothesized mechanism of action,” the researchers wrote. “Further study is warranted, in large samples and multiple sites, to confirm the effects of EFMT training, on specific symptom effects, and to explore mechanisms of action via neuroimaging the brain changes that are associated with EFMT.”

Neuroimaging the mechanisms of EFMT was exactly the goal of the data recently presented in New York. Here, a team provided a small sample of 14 MDD patients with six weeks of EFMT training and then, using functional MRI, observed changes in key regions of the brain when performing an abbreviated version of the intervention. The team noted increases in effective connectivity between regions of the brain that process cognitive control and emotion processing that, importantly, correlated positively with reductions in MDD symptoms.

In a statement, Dr. Sophia Frangou, a professor of psychiatry at ISMMS and the senior collaborator on the study, described the findings as “initial evidence that cognitive-emotional training may be associated with changes in brain plasticity in the networks implicated in MDD. … This helps us understand how EFMT has its effect in patients with MDD.”

The findings of these investigations were supported by a clinical pilot study that combined the EFMT intervention with tDCS, a form of neurostimulation with evidence of treating depression. Among the 17 participants who completed the six-week pilot, the researchers found the dual treatment to be feasible and safe. Further, 41 percent of the participants met the clinical response cutoff, with responders demonstrating improved recognition for fear and surprise over those who did not show a response.

“This study provides preliminary evidence that tDCS combined with cognitive-emotional training has great potential as a novel method for optimizing the antidepressant efficacy of tDCS in medication resistant depression patients, which is sorely needed for this difficult-to-treat population,” Dr. Colleen Loo, a professor of psychiatry at the University of New South Wales and the senior study author, said in a statement.

In a statement released by Click regarding these study results, CEO David Benshoof Klein described his company and collaborator Magellan Health’s eventual plans to bring the digital therapeutic to market as a prescription medical treatment for depression.

“Click has met with FDA to confirm the regulatory and clinical pathway, and will seek clearance as a class II medical device with a treatment claim following a pivotal study that will commence shortly,” he said. “In addition, we are collaborating with our strategic investor, Magellan Health, on this effort. Our high quality data combined with Magellan’s expertise in clinical impact, behavioral health and reimbursement will help ensure that the program is available to those patients in need upon clearance from FDA.”