Acute Migraine Drug Hits Co-primary Endpoints in Phase 3 Trial

Deborah Brauser

January 03, 2020

Topline results from the phase 3 MOMENTUM trial show the experimental migraine drug AXS-07 (Axsome Therapeutics) met both of its co-primary endpoints plus several key secondary outcomes, the manufacturer has announced.

Results from the study, which included almost 1600 adult patients with prior inadequate response to acute migraine treatment, showed that significantly more of the participants who received the study drug achieved greater freedom from pain and absence from most bothersome symptom 2 hours posttreatment vs those who received matching placebo.

In a US Food and Drug Administration (FDA) Special Protocol Assessment (SPA), the group receiving AXS-07 also achieved greater sustained pain freedom 2 to 24 hours posttreatment, greater and more sustained migraine relief, and a greater reduction in use of rescue medication than a group receiving the selective serotonin receptor agonist rizatriptan, demonstrating superiority to an active comparator treatment.

"Given that rizatriptan is one of the most effective triptans and that the study enrolled patients with difficult-to-treat migraine, this finding is impressive," Richard B. Lipton, MD, professor, vice chair of neurology, and director of the Montefiore Headache Center, Albert Einstein College of Medicine, New York City, said in a press release from the manufacturer.

"The results of this study suggest that AXS-07 may provide an important treatment option for people with difficult-to-treat migraine," added Lipton, who is a past president of the American Headache Society.

The manufacturer notes that, on the basis of the trial's results, a new drug application (NDA) filing to the FDA for the acute treatment of migraine is anticipated for the second half of this year.

Efficacy Endpoints Met

AXS-07 is a rapidly absorbed oral "multi-mechanistic investigational medicine," Axsome noted in its release. It consists of 20 mg of MoSEICTM [molecular solubility enhanced inclusion complex] meloxicam and 10 mg of rizatriptan.

The drug "is thought to act by inhibiting CGRP release, reversing CGRP-mediated vasodilation, and inhibiting neuro-inflammation, pain signal transmission, and central sensitization," the company added. "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 trial investigators sought to assess treatment of a single migraine attack of moderate or severe intensity by comparing four groups randomly assigned in a 2:2:2:1 ratio: those receiving AXS-07, the meloxicam or the rizatriptan alone, or placebo.

The researchers enrolled a total of 1594 participants. The study population had an average score of 3.6 on the Migraine Treatment Optimization Questionnaire, signifying poor response to prior acute treatments.

In addition, the majority of patients (75.4%) had allodynia (pain from normally nonpainful stimuli). Many were also obese (43.7%) and reported experiencing severe intensity migraine pain (41.2%) and/or morning migraines (36.6%).

Results showed that a significantly greater percentage of participants receiving AXS-07 achieved pain freedom 2 hours after dosing vs those receiving placebo (19.9% vs 6.7%, respectively; P < .001). More of this group also achieved freedom from most bothersome symptom: nausea, photophobia, or phonophobia (36.9% vs 24.4%, P = .002).

"Superiority of AXS-07 to rizatriptan and MoSEIC meloxicam (component contribution) was established as specified in the SPA," by showing a greater percentage of its group achieving sustained freedom from pain 2 to 24 hours after treatment (16.1% vs 11.2%, P = .04; and 16.1% vs 8.8%, P = .001; respectively), the manufacturer notes. The percentage of the AXS-07 group achieving this endpoint was also significantly greater than in the placebo group (5.3%, P < .001).

AXS-07 also met several other key secondary outcomes vs rizatriptan and placebo, as shown in the following table.

Table. Secondary Outcomes, Compared with the AXS-07 Group

Outcome

AXS-07

Rizatriptan

Placebo

Sustained pain relief 2-24 hours post-dose

53.3%

43.9%

(P = .006)

33.5%

(P < .001)

Sustained pain relief 2-48 hours post-dose

46.5%

36.5%

(P = .003)

31.1%

(P < .001)

Pain relief 1.5 hours post-dose

60.5%

52.5%

(P = .02)

48.3%

(P = .004)

Use of rescue medication

23%

34.7%

(P < .001)

43.5%

(P < .001)

 

Compared with those receiving rizatriptan, the patients receiving AXS-07 also showed greater improvement on the Patient Global Impression of Change scale (P = .02) and a greater percentage of returning to normal functioning at 24 hours (P = .03).

The most commonly reported adverse events (AEs) for the group receiving the novel study drug were nausea, dizziness, and somnolence. However, none of these AEs occurred in more than 3% of the group or at a rate greater than in the placebo group.

Although one serious AE occurred in the AXS-07 group, the researchers deemed it to not be treatment-related.

"These data have potentially important implications for patient care based on the high rate of inadequate response to, and patient dissatisfaction with, current treatments," Herriot Tabuteau, MD, chief executive officer of Axsome, said in the release.

"Based on FDA feedback, Axsome believes that MOMENTUM will be the only efficacy trial required to support an NDA filing for AXS-07 for the acute treatment of migraine," the manufacturer added.

The drug is also being evaluated in the ongoing phase 3 INTERCEPT trial; however, participants in that study are to administer it at the earliest sign of migraine pain.

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