FDA Grants First-in-Class Marketing Authorization for Digital Therapeutic in Episodic Migraine Prevention

The US FDA has granted marketing authorization for CT-132, the first prescription digital therapeutic (PDT) indicated for the preventive treatment of episodic migraine in adults. Developed by Click Therapeutics, the smartphone-based application received authorization via the De Novo pathway for first-in-class medical devices on April 15, 2025, according to the company.1

CT-132 is indicated for adjunctive use alongside acute and/or other preventive migraine treatments in patients 18 years and older. The authorization was supported by data from 2 randomized controlled trials that demonstrated efficacy of the the digital therapeutic when used concurrently with standard migraine pharmacotherapy.1

"This marks a significant milestone for the more than 37 million adults in the US who live with migraine," Shaheen Lakhan, MD, PhD, chief medical and scientific officer of Click Therapeutics, said in a statement. "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."1

Pivotal Trials

The pivotal phase 3 ReMMi-D (Reduction in Monthly Migraine Days, NCT05853900) registration trial2 evaluated 558 individuals with migraine receiving standard-of-care migraine medications. Results showed CT-132 met its primary endpoint with a statistically significant reduction in monthly migraine days (MMDs) after 12 weeks compared to a sham digital control (treatment difference: –0.9 MMDs; P =.005). Participants in the treatment arm experienced a mean reduction of –3.04 MMDs by study completion.2

A second bridging study, ReMMiD-C (NCT06004388), demonstrated similar performance specifically in individuals taking at least 1 calcitonin gene-related peptide (CGRP) inhibitor.2 Both trials were designed to mirror contemporary pharmacologic migraine studies but uniquely allowed patients to continue their existing medication regimens without washout periods in order to evaluate the additive effect of the digital therapeutic.

In the ReMMi-D registration trial, secondary endpoints showed improvements in migraine-related quality of life as measured by the Migraine-Specific Quality-of-Life Questionnaire (MSQ) from as early as 4 weeks and continuing through weeks 8 and 12 (P <.001 at both time points). The Migraine Disability Assessment (MIDAS) score showed greater improvement in the CT-132 arm compared to the sham arm at treatment conclusion, though these secondary analyses did not include multiplicity adjustment or formal hypothesis testing.

Notably, adherence to the investigational therapy was high throughout the 12-week treatment period, with a median of 84 out of 84 daily lessons completed by those receiving CT-132 compared to 81 lessons in the sham control group. The digital therapeutic was well-tolerated with no discontinuations due to treatment-emergent adverse events. The performance of CT-132 was similar among participants taking CGRP inhibitors in the ReMMiD-C bridging study, according to the statement.

The absence of contraindications positions CT-132 as a complementary intervention to existing migraine treatments. The device combines evidence-based behavioral therapies with proprietary mechanisms of action delivered through a smartphone application.

According to Stewart J. Tepper, MD, vice president, New England Institute for Neurology and Headache and scientific advisor to Click, "I think this is very exciting as a clinician who takes care of patients because we don't have anything like this in our migraine armamentarium. We know that behavioral techniques are helpful adjunctively, but large areas of the country just don't have access to them."

According to Click Therapeutics, CT-132 may be positioned for further development as a "software-enhanced drug™ therapy" under the FDA's draft guidance on Prescription Drug Use-Related Software (PDURS).

References
1. Click Therapeutics announces FDA marketing authorization for CT-132, the first prescription digital therapeutic for the preventive treatment of episodic migraine in the United States. News release. Click Therapeutics. April 15, 2025. Accessed April 16, 2025. https://www.clicktherapeutics.com/news/click-therapeutics-announces-fda-marketing-authorization-for-ct-132-the-first-prescription-digital-therapeutic-for-the-preventive-treatment-of-episodic-migraine-in-the-united-states
2. Click Therapeutics announces CT-132 met primary endpoint for the reduction of monthly migraine days in ReMMi-D pivotal trial. News release. Click Therapeutics. September 4, 2024. Accessed April 16, 2025. https://www.businesswire.com/news/home/20240904512812/en/Click-Therapeutics-Announces-CT-132-Met-Primary-Endpoint-for-the-Reduction-of-Monthly-Migraine-Days-in-ReMMi-D-Pivotal-Trial