The U.S. Food and Drug Administration (FDA) has approved CT-132, developed by Click Therapeutics, as the first prescription digital therapeutic (DTx) for the preventive treatment of episodic migraine in adults. This landmark authorization, granted through the FDA's De Novo pathway, is indicated for patients 18 years and older as an adjunctive therapy alongside acute and other preventive migraine treatments.
The approval represents a significant advancement for the more than 37 million American adults living with migraine, offering a novel, accessible treatment option that can be used anywhere via a smartphone application.
Clinical Evidence Supporting Approval
The FDA's decision was based on data from two double-blind, decentralized randomized trials: the phase 3 ReMMi-D trial (NCT05853900) and the supportive ReMMiD-C bridging study (NCT06004388).
In the pivotal ReMMi-D trial involving 568 patients with episodic migraine, CT-132 demonstrated statistically significant efficacy in reducing monthly migraine days (MMDs). After 12 weeks of treatment, patients using CT-132 experienced a reduction of 3.04 MMDs, which was 0.9 days better than the sham control group (p=.005).
Dr. Shaheen Lakhan, Chief Medical and Scientific Officer at Click Therapeutics, emphasized the significance of this approval: "As a groundbreaking digital therapeutic for migraine prevention, CT-132 offers eligible patients a new path to reducing the burden caused by migraine, one they can access anywhere via an evidence-based mobile application on their smartphone, significantly improving accessibility and expanding care to patients."
Mechanism of Action and Treatment Approach
CT-132 delivers a 12-week, app-based intervention that integrates multiple evidence-based behavioral techniques, including elements of cognitive behavioral therapy. The therapeutic targets the underlying neurobiology of migraine by modulating dysfunctional neurocircuitry—specifically the sensory, autonomic, and affective networks associated with the condition.
By strengthening neurolimbic circuitry, CT-132 aims to reduce the brain's hypersensitivity to internal and external stimuli, thereby decreasing the frequency of migraine attacks. Importantly, the digital therapeutic carries no contraindications in its label and is not intended as a standalone therapy or replacement for other migraine treatments.
Quality of Life Improvements
Beyond the reduction in migraine frequency, the ReMMi-D trial demonstrated significant improvements in patient quality of life measures. CT-132 treatment resulted in enhanced Migraine-Specific Quality-of-Life (MSQ) scores by weeks 8 and 12 (p<.001 at both time points), with noticeable gains emerging as early as week 4.
By the end of the treatment period, patients receiving CT-132 also showed categorical improvements on the Migraine Disability Assessment (MIDAS) questionnaire and reported significant health improvements as measured by Patient Global Impression-Change (p<.001).
The therapy was well-tolerated, with no treatment-related adverse events observed during the clinical trials. Both the CT-132 and sham groups showed nearly 100% median adherence to daily tasks, indicating strong patient engagement with the digital platform.
Expanding the Digital Therapeutic Landscape
The approval of CT-132 represents a boost for the digital therapeutic sector, which has faced challenges in establishing commercially successful prescription therapies. Some pioneers in the field, such as Pear Therapeutics and Better Therapeutics, have struggled to build viable businesses, partly due to the lack of a well-defined benefit category for these products in Medicare and Medicaid.
David Benshoof Klein, Chief Executive Officer at Click Therapeutics, noted the broader implications of this approval: "With this landmark, first-in-class FDA authorization in episodic migraine, Click's interventions have now demonstrated clinically meaningful benefit across three unique therapeutic areas, including psychiatry, cardiometabolic disease, and now neurology. As the first authorization in our neurology pipeline, and the first of our PDTs to target and successfully treat a pain-related condition, it confirms the power of Click's platform to deliver meaningful outcomes across therapeutic areas."
Patient Selection and Complementary Treatment
The ReMMi-D trial enrolled patients with at least a one-year history of migraine, confirmed by ICHD-3 criteria, who were using at least one prescription acute or preventive treatment. Individuals on anti-CGRP therapies were excluded from this study.
To complement the pivotal data, the ReMMiD-C bridging study specifically evaluated CT-132 in 110 patients who were receiving calcitonin gene-related peptide (CGRP) therapy. This additional study provided supportive information on the digital therapeutic's effectiveness when used alongside these newer migraine preventive medications.
Addressing an Unmet Need in Migraine Care
Episodic migraine, characterized by headaches occurring on fewer than 15 days per month, represents a significant burden for patients. The approval of CT-132 offers a non-pharmacological option that can be integrated into existing treatment regimens, potentially improving outcomes without adding medication-related side effects.
As the first digital therapeutic approved for migraine prevention, CT-132 may help address gaps in care by providing an accessible intervention that patients can use between clinical visits, potentially improving treatment adherence and outcomes in this challenging neurological condition.
