FDA clears first DTx for depression from Otsuka, Click

Otsuka and Click Therapeutics’ Rejoyn has become the first prescription digital therapeutic (DTx) to be approved by the FDA for people with major depressive disorder.

Rejoyn (formerly CT-152), a software-as-a-medical device (SaMD) delivered via a smartphone app, has been authorised as an add-on to clinician-managed outpatient care for adults aged 22 and over with MDD who require antidepressant medicines.

Delivered over six weeks, the DTx is designed to help alleviate MDD symptoms using a combination of cognitive emotional training exercises and brief therapeutic lessons. It is due to be available for download from app stores for iOS and Android in the second half of this year.

Rejoyn is the first fruit of a collaboration set up in 2019 with Otsuka, worth $300 million, focusing on the development of DTx software for MDD. In 2021, the pair teamed up with Verily, the healthcare subsidiary of Google owner Alphabet, to run the pivotal Mirai study of Rejoyn in 286 people with MDD.

In the study, participants aged 22 to 64 were randomised to either Rejoyn or a sham control app as an addition to their antidepressant medication. The DTx includes three components, namely cognitive behavioural therapy (CBT) sessions, emotional faces memory task (EFMT) exercises, and personalised reminders and messaging.

Treatment with Rejoyn met the primary endpoint with a significant mean change from baseline to week six in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, achieving an average 8.78-point reduction versus 6.66 points for the sham group. Symptom improvement was also reported, based on patient- and clinician-reported outcome surveys.

Describing Rejoyn as “physical therapy for the brain”, Click’s scientific advisor Brian Iacoviello of Icahn School of Medicine – a co-inventor of the EFMT test – said the app was designed to help improve connections in the brain regions affected by depression.

“When stronger and more balanced connections are created, the regions of the brain responsible for processing and regulating emotions are better able to work together and symptoms of depression can improve,” he added.

Click hopes to position Rejoyn as a way to enhance the efficacy of antidepressants, saying that only around a third of patients with MDD respond to the first medication tried.

The company’s chief executive, David Benshoof Klein, said it “provides hope for those who are looking for new treatment options, especially one that is easily accessible through the device in the palm of your hand.”

Regulatory approval could only be the first hurdle facing Click and Otsuka, however, as some DTx developers have struggled to build a sustainable commercial business, in part because of uncertain reimbursement pathways.

That has driven some into bankruptcy, notably Pear Therapeutics, which saw its assets sold off last year to various other companies, including Click. Others have been forced to refocus their business operations, such as Akili, which has retreated from the prescription business in favour of a direct-to-consumer (DTC) model.

Last year, US lawmakers reintroduced the Access to Prescription Digital Therapeutics Act, which would create a dedicated benefit category for these products in Medicare and Medicaid, but that has not yet made it onto the statute.

Click is also working on DTx candidates for schizophrenia with Boehringer Ingelheim and with Indivior on software to support people with substance use disorders. Its in-house pipeline is led by a DTx candidate for migraine.