AXS-07 demonstrates efficacy against migraine in phase 3 trials

In the phase 3 MOMENTUM and INTERCEPT trials, the investigational migraine drug AXS-07 met its coprimary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours compared with placebo.

The results were presented at the Annual Meeting of the American Neurological Association.

MOMENTUM

AXS-07 (Axsome Therapeutics) is an oral medication that consists of MoSEIC meloxicam and rizatriptan. Researchers hypothesize that AXS-07 inhibits CGRP release, “reversing CGRP-mediated vasodilation and inhibiting neuro-inflammation, pain signal transmission and central sensitization,” according to Cedric O'Gorman MD, MBA, senior vice president of Clinical Development and Medical Affairs at Axsome, and colleagues. The MoSEIC technology accelerates meloxicam absorption, they added.

For the MOMENTUM trial, O’Gorman and colleagues compared the safety and efficacy of a single dose of AXS-07 with its individual components and placebo. Overall, 1,594 adults with a history of inadequate response to previous acute migraine treatments were randomly assigned to one of four treatment arms: AXS-07 (20 mg meloxicam plus 10 mg rizatriptan; n = 456), MoSEIC meloxicam (10 mg; n = 456), rizatriptan (10 mg; n = 456) or placebo (n = 227).

O’Gorman and colleagues reported that AXS-07 was associated with significant improvements in pain freedom (19.9% vs. 6.7%) and freedom from most bothersome symptom (36.9% vs. 24.4%) after 2 hours of dosing compared with placebo. It was also significantly superior to rizatriptan alone and MoSEIC meloxicam alone in sustaining pain freedom (16.1% vs. 11.2% and 8.8%, respectively) and significantly superior to rizatriptan in providing pain relief after 1 hour (44% vs. 37%).

The use of rescue medication was lower among patients who received AXS-07 (23%) vs. those who received rizatriptan (34.7%) meloxicam (35.1%) and placebo (43.5%).

AXS-07 was “generally safe and well tolerated,” according to O’Gorman and colleagues. The most common adverse events associated with the treatment included nausea, dizziness and somnolence, none of which occurred at a greater rate than placebo or in more than 3% of patients.

INTERCEPT

In the INTERCEPT trial, researchers randomly assigned 302 patients in a 1:1 ratio to a single dose of AXS-07 or placebo at the earliest sign of migraine pain, “while the pain was still mild,” according to researchers.

As Healio previously reported, AXS-07 met both coprimary endpoints — significant improvements in pain freedom (32.6% vs. 16.3%) and freedom from most bothersome symptom (43.9% vs. 26.7%) compared with placebo at 2 hours. In addition, patients who received AXS-07 were significantly more likely to achieve sustained freedom from pain up to 24 hours (22.7% vs. 12.6%) and 48 hours (20.5% vs. 9.6%) after dosing, as well as sustained freedom from pain progression up to 24 hours (73.5% vs. 47.4%) after dosing compared with placebo.

AXS-07 also reduced the need for rescue medication, with 15.3% of patients in the AXS-07 group using rescue medication within 24 hours of dosing vs. 42.2% of patients in the placebo group.

Safety data were consistent with findings from the MOMENTUM trial.

During a webcast in April, Herriot Tabuteau, MD, CEO of Axsome, said a long-term, open-label trial further evaluating AXS-07 in more than 700 patients is ongoing. He also said the company plans on filing a new drug application for AXS-07 in the fourth quarter of this year.

References:

• Jones A, et al. Poster #215. Presented at: American Neurological Association Annual Meeting; Oct. 4-9, 2020 (virtual meeting).
• O’Gorman C, et al. Poster #219. Presented at: American Neurological Association Annual Meeting; Oct. 4-9, 2020 (virtual meeting).