Voice-over: Welcome to Spotlight on Migraine, hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease.
In this episode, Dr. Cedric O’Gorman, from Axsome Therapeutics, reports on efficacy and safety data for their pipeline acute medication AXS-07, which is a combination of the NSAID meloxicam and rizatriptan.
Dr. Cedric O’Gorman: Good morning. My name is Dr. Cedric O’Gorman, and I’m senior vice-president of clinical development and medical affairs at Axsome Therapeutics. Today, I will be presenting the results of the Phase 3 MOMENTUM trial, which evaluated the efficacy and safety of AXS-07, Axsome’s novel oral multi-mechanistic investigational medicine for the acute treatment of migraine in patients with a history of inadequate response to prior acute migraine treatments.
The seriousness of migraine is underappreciated. The World Health Organization classifies severe migraine attacks among the most disabling illnesses, comparable to dementia, quadriplegia, and active psychosis. Migraine damages family life, social life, and employment.
A significant percentage of patients experience inadequate response to current acute migraine treatments, and this suboptimal treatment has serious consequences, as large-scale studies show that in addition to the debilitating pain, it can lead to increased progression from episodic to chronic migraine. There’s therefore an urgent need for new treatments that provide improved efficacy for this serious neurological disease.
AXS-07 is a novel oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine, consisting of MoSEIC meloxicam and rizatriptan. AXS-07 is thought to act by inhibiting CGRP release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain-signal transmission, and central sensitization. Axsome’s MoSEIC technology significantly increases the speed of absorption of the meloxicam component after oral administration, while maintaining a long plasma half-life.
The MOMENTUM — or “maximizing outcomes in treating acute migraine” — study was a Phase 3 randomized, double-blind, multicenter, active-and-placebo-controlled trial to assess the efficacy and safety of AXS-07 in the acute treatment of moderate and severe migraine in adults. Only migraine sufferers with a history of inadequate response to prior acute migraine treatments, as assessed by the Migraine Treatment Optimization Questionnaire, or mTOQ-4, were enrolled. A total of 1,594 subjects were randomized in a 2:2:1 ratio to receive a single dose of AXS-07, MoSEIC meloxicam, rizatriptan, or placebo following a qualifying migraine of moderate or severe intensity.
The co-primary endpoints of the study were pain freedom at two hours and freedom from the patient’s most bothersome migraine-associated symptom — photophobia, nausea, or phonophobia — at two hours for AXS-07, as compared to placebo. The key secondary endpoint to establish component contribution was sustained pain freedom from 2 to 24 hours after dosing for AXS-07, as compared to rizatriptan and MoSEIC meloxicam.
Shown here are the key inclusion criteria. In addition to history of inadequate response to prior acute migraine treatments, eligible patients were required to have an average of two to eight moderate or severe migraine attacks per month.
The baseline demographics and the clinical characteristics of the MOMENTUM study population are shown on this slide. Overall, demographics and baseline characteristics were consistent across treatment groups. Importantly, approximately 40 percent of patients described prior triptan use.
The characteristics of the patients enrolled reflect a population with very difficult-to-treat migraine. The mean mTOQ-4 score was 3.6 out of a maximum of 8, reflecting patients who are categorized as poor responders to prior acute migraine treatments.
In addition to a history of inadequate response, enrolled patients exhibited a high rate of characteristics that are strongly associated with poor treatment outcomes, including cutaneous allodynia, which was seen in 75 percent of patients; severe migraine pain intensity, which was seen in 41 percent of patients; obesity, which was seen in 43.4 percent; and morning migraine, seen in 36.4 percent. Of note, a greater percentage of patients in the AXS-07 group had cutaneous allodynia and severe migraine pain as compared to the rizatriptan group.
Now to the efficacy results. On the first co-primary endpoint of pain freedom at two hours, a statistically significantly greater proportion of patients treated with AXS-07 were pain free as compared to placebo — 19.9 percent versus 6.7 percent, respectively — for a placebo-adjusted difference of 13.2 percent and a P value of less than 0.001.
On the second co-primary endpoint of freedom from the patient’s most bothersome migraine-associated symptom, a statistically significantly greater proportion of patients treated with AXS-07 were free of their most bothersome symptom at two hours as compared to placebo — 36.9 percent versus 24.4 percent, respectively — for a placebo-adjusted difference of 12.5 percent and with a P value of 0.002.
On the key secondary endpoint of sustained pain freedom from 2 to 24 hours, evaluated in order to establish component contribution, a statistically significantly greater proportion of patients treated with AXS-07 had sustained pain freedom as compared to rizatriptan and MoSEIC meloxicam — 16.1 percent for AXS-07 versus 11.2 percent for rizatriptan, with a P value of 0.038, versus 8.8 percent with MoSEIC meloxicam, with a P value of 0.001. AXS-07 was also statistically significant versus placebo on this measure, with a P value of less than 0.001.
AXS-07 provided substantial and rapid relief of migraine pain, as shown on this slide. The percentage of patients achieving pain relief with AXS-07 was numerically greater than with rizatriptan at every time point starting at 15 minutes and statistically significant by 60 minutes. This performance over rizatriptan is significant since rizatriptan is widely recognized as the fastest-acting and one of the most potent, effective oral triptans.
This slide shows the pain freedom rates over time starting two hours after dosing. AXS-07 resulted in a consistently greater proportion of patients experiencing pain freedom compared to all comparators, with the benefit provided by AXS-07 increasing over time.
AXS-07 demonstrated statistical significant superiority over rizatriptan on multiple secondary outcome measures in addition to rapid one-hour pain relief, sustained pain relief, and sustained pain freedom, as shown on the prior slides. These efficacy benefits of AXS-07 translated into statistically significant less use of rescue medication with AXS-07 as compared to rizatriptan, with only 23 percent of AXS-07–treated patients requiring the use of rescue medication after one single dose of study medication, versus 35 percent of rizatriptan patients, with a P value of less than 0.001.
AXS-07 was also superior to rizatriptan on the patient global impression of change — or PGI-C — scale, with a P value of 0.022. The therapeutic benefits of AXS-07 translated into important functional advantages, with a statistically significantly greater proportion of patients treated with AXS-07 returning to normal functioning at 24 hours, as compared to those treated with rizatriptan, with a P value of 0.027.
AXS-07 was safe and well tolerated in this study. The most commonly reported adverse events with AXS-07 were nausea, dizziness, and somnolence, none of which occurred at a rate greater than placebo or greater than 3 percent. There was one serious adverse event of miscarriage that occurred in the AXS-07 arm, which was deemed non–treatment-related.
In summary, in the Phase 3 MOMENTUM trial, treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant efficacy as compared to rizatriptan and placebo in the acute treatment of migraine in patients with a history of inadequate response to prior treatments. AXS-07 met the co-primary endpoints of pain freedom and freedom from most bothersome symptoms at two hours compared to placebo.
The low placebo response for pain freedom at two hours, 6.7 percent, reflects the difficult-to-treat patient population this study aimed to enroll. Statistically significant superiority of AXS-07 over rizatriptan was observed for pain freedom at one hour, sustained pain freedom, and sustained pain relief. These efficacy benefits of AXS-07 translated into statistically significantly better patient global assessment of response, greater return to normal functioning, and significantly reduced rescue medication use for AXS-07–treated patients as compared to those with rizatriptan. AXS-07 was generally safe and well tolerated in this study.
In conclusion, the multi-mechanistic approach of AXS-07 may represent a novel treatment for patients that is superior to current standard of care. The enhanced efficacy of AXS-07 may be especially relevant for patients with more-difficult-to-treat migraine.
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*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.