Eric Baron, DO, on the Approval of CT-132: A Digital Shift in Migraine Care

Eric Baron, DO

There have been several notable advances in the treatment of migraine over the last decade, namely with the introduction and expansion of calcitonin gene-related peptide (CGRP)-targeting therapeutics. As technology continues to reach new heights, the possibilities of digital therapeutics have emerged as a promising approach to treating neurologic conditions like migraine.

In mid-April, the migraine community saw its first FDA-approved digital treatment reach market, as the agency gave greenlight to Click Therapeutics’ CT-132, an app-based program. The treatment, approved through the De Novo pathway, is indicated for patients aged 18 years and older, and is intended for adjunctive use alongside acute and/or other preventive treatments for migraine. Delivered over a 12-week period, the intervention uses several evidence-based behavioral techniques, including elements of cognitive behavioral therapy.

Following the approval, neurologist Eric Baron, DO, of Cleveland Clinic’s Neurological Institute, discussed the significance of what this new medication means for patients and clinicians alike in the migraine community. In addition, he spoke on the major trials and evidence that led to CT-132’s approval, its additive benefit alongside current medications, and its potential to empower patients with a non-drug option. Furthermore, Baron spoke on how clinicians can effectively implement this therapy in practice and offered guidance on which patients may benefit most.

NeurologyLive: Describe your reaction to the approval; what does this mean for both patients and clinicians alike?

Eric Baron, DO: The FDA authorization of CT-132 is a groundbreaking milestone in migraine management, introducing a first-in-class prescription digital therapeutic (PDT) that expands the migraine treatment landscape.

For patients, this offers a novel, non-pharmacological option that is accessible via smartphone, delivering personalized care with minimal side effect potential. It empowers patients to actively manage their condition, potentially reducing migraine frequency and improving quality of life.

For clinicians, CT-132 adds a rigorously tested tool to their arsenal, addressing gaps in care where traditional pharmacotherapy alone falls short. This approval signals a shift toward integrating digital solutions into standard care, promising enhanced outcomes and greater patient engagement.

Discuss the data from the phase 3 studies that led to its approval; what stood out from an efficacy and safety standpoint?

This is the first migraine digital therapeutic to be studied with this degree of rigor, in twoPhase III multicenter, double-blind, randomized controlled trials, leading to FDA authorization of CT-132 for episodic migraine prevention.

The two Phase III trials were ReMMi-D (pivotal) and ReMMiD-C (bridging) for reducing the number of monthly migraine days (MMDs) compared to a sham digital control (a digital control app). ReMMi-D was the main study that included patients on commonly prescribed migraine preventive medications; ReMMiD-C was a bridging study that provided supportive information to ReMMi-D including those on newer CGRP antagonist medications.

The study designs mirrored those of typical randomized control trials for migraine medications but allowed patients to continue their existing migraine medications without any washout period and included acute medications (i.e. NSAIDS, triptans) and/or first- and second-line (or non-specific) preventatives (i.e. propranolol, topiramate). So the additive treatment benefit of CT-132 on top of background pharmacotherapy was better evaluated this way. The studies confirmed evidence in support of the safety and effectiveness of CT-132.

ReMMi-D was the 12 week pivotal trial with 570 patients and achieved a statistically significant reduction in monthly migraine days (MMDs): -3.04 MMDs in the CT-132 group vs. -0.9 MMDs for the sham control (P = 0.005), along with other improvements including Migraine-Specific Quality-of-Life Questionnaire (MSQ) scores, Migraine Disability Assessment (MIDAS) scores, and Positive Patient Global Impression - Change (PGI-C) scores. No treatment-related adverse events were reported, highlighting CT-132’s favorable safety profile as a software-only intervention.

To establish broader clinical applicability of CT-132, the ReMMiD-C study bridged the pivotal ReMMiD study with patients taking the new-class of migraine-specific medications, CGRP inhibitors. ReMMiD-C was also a 12-week trial of 110 patients who were treated with one or more CGRP inhibitors for preventive or acute treatment of episodic or chronic migraine. It showed CT-132’s additive benefit across all migraine medications, including CGRP inhibitors. No adverse events or discontinuations due to treatment-emergent issues were observed, reinforcing CT-132’s safety.

What stood out to me:

Efficacy: The significant MMD reduction (-3.04 days) and early, sustained quality-of-life improvements underscore CT-132’s ability to enhance outcomes beyond pharmacotherapy alone. Its compatibility with both standard and newer CGRP inhibitors broadens its applicability.

Safety: The absence of treatment-related adverse events is a major advantage, especially compared to medications with potential side effects, making CT-132 a low-risk adjunctive option.

What types of conversations need to be had among clinicians to their patients about this new therapeutic?

When I see patients in clinic, I like to discuss all available options to let them feel like they have a lot of options, and that they know I value their treatment preferences. So clinicians should initiate open, patient-centered discussions about CT-132. Those discussions should include the following points.

• Explain the Modality: Describe CT-132 as a prescribed, FDA-authorized digital therapeutic delivered via smartphone, designed to reduce migraine frequency by targeting brain hypersensitivity through neuromodulatory exercises.
• Set Expectations: Highlight that CT-132 is a 12-week program requiring 5-10 minutes daily, with potential benefits like fewer migraine days and improved quality of life. Emphasize its complementary role with existing medications.
• Address Accessibility: Note that it’s smartphone-based, making it widely accessible, and discuss how personalized SMS and symptom tracking support adherence.
• Discuss Safety: Reassure patients about the lack of medication-like side effects, making it a low-risk option.
• Empower Patients: Frame CT-132 as a tool to enhance control over their condition, teaching skills to mitigate migraine impact and improve daily functioning.

As a neurology community, how can we better welcome digital therapeutics?

To better integrate PDTs like CT-132, I would suggest a number of steps that the neurology community could consider:

1. Education and Training: Incorporate PDT education into medical training and continuing education to familiarize clinicians with their mechanisms, evidence, and applications. Workshops or webinars can demystify digital therapeutics.
2. Collaboration with Developers: Partner with companies like Click Therapeutics to provide real-world feedback, ensuring PDTs align with clinical needs and patient realities.
3. Advocacy for Reimbursement: Push for insurance coverage and reimbursement policies to make PDTs financially accessible, addressing cost barriers.
4. Research and Evidence Sharing: Encourage further studies to expand indications and share trial data at conferences to build trust in PDT efficacy and safety.
5. Patient-Centered Integration: Develop guidelines for incorporating PDTs into treatment plans, emphasizing shared decision-making to align with patient preferences and technological comfort.
6. Technology Infrastructure: Support practices in adopting digital tools, such as secure platforms for prescribing and monitoring PDT use, to streamline integration.

Do you foresee certain types of patients who may be best suited with CT-132?

Personally, I always tell patients the less medicine the better. Most patients also prefer non-pharmaceutical options if they can remain controlled without them. However, most patients will need to add these conservative strategies to medications for optimal control. So with that said, CT-132 has broad potential, but certain patient profiles may particularly benefit such as:

• Patients with Suboptimal Medication Response: Those experiencing frequent migraines despite adherence to acute or preventive medications (e.g., NSAIDs, triptans, or CGRP inhibitors) could see additive benefits from CT-132’s neuromodulatory approach.
• Tech-Savvy Individuals: Patients comfortable with smartphones and open to digital interventions may engage more readily with CT-132’s daily exercises and tracking features.
• Those Seeking Non-Pharmacological Options: Patients wary of medication side effects or preferring non-drug therapies may appreciate CT-132’s safety profile and behavioral focus.
• Individuals with Limited Access to Behavioral Therapies: Patients in areas with few trained clinicians for cognitive or biobehavioral interventions can access CT-132’s evidence-based techniques remotely.
• Highly Motivated Patients: Those eager to take an active role in managing their condition may thrive with CT-132’s empowering, skill-building approach.