IOR-03 - Efficacy and Safety of Symbravo® (MoSEICTM meloxicam and rizatriptan) in Participants With Migraine Experiencing an Inadequate Response to Oral CGRP Inhibitors: Topline Results From the EMERGE Trial

One Sentence Summary : In the open-label EMERGE trial in participants experiencing inadequate response to oral CGRP inhibitors, treatment with Symbravo^® (MoSEIC^TM meloxicam and rizatriptan [mMR]) was associated with improved migraine treatment response relative to the pretreatment baseline, including higher reported rates of pain freedom, sustained pain relief, functional recovery, and improved quality of life.

Background:

Symbravo^® (MoSEIC^TM meloxicam and rizatriptan [mMR]) was recently approved by the FDA for the acute treatment of migraine. The efficacy and safety of mMR were demonstrated in three Phase 3 clinical studies, MOMENTUM, INTERCEPT and MOVEMENT. Oral calcitonin gene-related peptide (CGRP) inhibitors (gepants) are a newer class of medication approved for the acute treatment of migraine. Here we report the topline results from the EMERGE study, which evaluated the efficacy and safety of mMR in participants who were undergoing treatment with a gepant for ≥1 month and experiencing an inadequate response to the gepant.

Methods:

EMERGE (NCT05550207) was a Phase 3, open-label, multicenter trial to evaluate the efficacy and safety of mMR in the acute treatment of migraine in adult participants experiencing inadequate response to a gepant. The diagnosis of migraine was per International Classification of Headache and Disorders-3 criteria. Eligible participants must have been using a gepant for the acute treatment of migraine for at least 1 month prior to enrollment (having treated at least 4 migraines with a gepant) and have had an inadequate response to the gepant. An inadequate response was defined as a score of ≤7 on the Migraine Treatment Optimization Questionnaire-4 (mTOQ-4), including a score of 1 (less than half the time) or 0 (never or rarely) when asked about the frequency of achieving pain freedom 2 hours after taking migraine medication. Participants were switched from their gepant to mMR and treated their next 4 migraine attacks with mMR over up to 8 weeks. The primary efficacy endpoint was the change in mTOQ-4 total score from baseline, while on the gepant, to the end of the mMR treatment period.

Results:

EMERGE enrolled 96 participants, who treated a total of 365 migraine attacks with mMR. The study met the primary endpoint by demonstrating statistically significantly greater migraine treatment response with mMR compared to treatment response with prior gepants, as assessed by the mTOQ-4 total score (5.2 versus 2.8, p< 0.001). On each of the four items of the mTOQ-4 questionnaire, statistically significantly greater proportions of patients achieved a clinical response (a score of 2 - “half of the time or more”) with mMR in comparison with baseline (while on a gepant). Specifically, pain freedom within 2 hours for most attacks was reported by 47.9% vs 1.0% (p< 0.001); sustained pain relief of 24 hours or more following a single dose of medication by 47.9% vs 16.7% (p< 0.001); ability to return quickly to normal activities by 51.0% vs 11.5% (p< 0.001), and feeling comfortable with their medication to plan daily activities by 63.5% vs 26.0% (p< 0.001). Across all attacks treated with mMR, 2-hour pain relief was reported for 50% of attacks, while 2-hour pain freedom was reported for 22.5% of attacks. Freedom from the most bothersome symptom was reported for 26.6% of attacks 2 hours post dose.

Moreover, mMR led to a statistically significant improvement in quality of life and daily functioning, assessed by the three domains of the Migraine-Specific Quality of Life Questionnaire (p=0.003 to < 0.001, compared to the gepant period). Additionally, participants reported overall improvement (minimally/much/very much improved) of migraine with mMR 30 minutes post-dose for 26.0% of attacks, as measured by the Patient Global Impression of Change, with improvement reported 2 hours post dose for 69.2% of attacks.

The safety and tolerability profile of mMR was consistent with previous trials. The most reported adverse events (≥2%) were fatigue (3.1%), nausea (3.1%), vomiting (2.1%), muscle tightness (2.1%), and dizziness (2.1%).

 

Conclusion:

In the EMERGE trial in participants experiencing and inadequate response to gepants, treatment with mMR was associated with significant improvements in migraine treatment response, including higher rates of rapid and sustained relief and improved functional recovery, as assessed by the mTOQ-4, and quality of life. In this population, treatment with mMR was associated with rapid and sustained relief of migraine pain and associated symptoms, with efficacy experienced as early as 30 minutes post dose. These results align with findings from the prior phase 3 studies, providing additional evidence for the efficacy of mMR across a range of migraine patient populations with varying pain intensities and prior responses to acute treatments.