Axsome's Novel AXS-07 Formulation Effective Against Migraine in Pooled Phase 3 Study Analysis
The novel meloxicam/rizatriptan combination is thought to act via CGRP inhibition and provided significant and sustained headache pain freedom in both studies.
In the phase 3 MOMENTUM and INTERCEPT studies, patients treated with AXS-07 saw reductions in headache pain freedom, most bothersome symptoms, and use of rescue medications.
At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18 in Denver, Colorado, presented data from a pooled analysis of the phase 3 MOMENTUM (NCT03896009) and INTERCEPT (NCT04163185) trials indicated that AXS-07 (Axsome Therapeutics) was effective at acutely treating migraine. All told, treatment with the investigational agent resulted in significant reductions in headache pain freedom, migraine symptoms, and rescue medication use.1
AXS-07, a novel, oral, rapidly absorbed, multi-mechanistic medicine, is thought to act by inhibiting calcitonin gene-related peptide (CGRP) release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain signal transmission, and central sensitization. In the pooled analysis, results showed that AXS-07 demonstrated greater headache pain freedom (23% vs 11%; P <.001) and absence of the most bothersome symptom (MBS)(39% vs 25%; P <.001) at 2 hours compared with placebo.
The investigational agent consists of MoSEIC (Molecular Solubility Enhanced Inclusion Complex) meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by MoSEIC technology, which results in rapid absorption of meloxicam while maintaining a long plasma half-life. AXS-07 remains investigational, as the FDA issued Axsome a complete response letter for its new drug application submission in May 2022, citing issues related to the chemistry, manufacturing, and controls considerations.
The analysis, led by Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, showed that patients on AXS-07 had improved sustained pain freedom between 2 and 24 hours (18% vs 8%; P <.001) and 48 hours (16% vs 7%; P <.001). In addition, 43% of AXS-07-treated patients had reduced rescue medication use through 24 hours vs 21% of those on placebo (P <.001). Notably, a higher rate of patients on the investigational agent returned to normal functioning in comparison with placebo starting at 1-hour post-dose.
MOMENTUM and INTERCEPT were the 2 main studies behind the 2022 new drug application submission of AXS-07. In MOMENTUM, 1594 patients with migraine were randomly assigned 2:2:2:1 to AXS-07, 10-mg rizatriptan, MoSEIC 20-mg meloxicam, or placebo, to treat a single migraine attack of moderate or severe intensity. INTERCEPT included 302 patients with migraine who were randomly assigned to either AXS-07 (n = 152) or placebo (n = 150) at the earliest onset of migraine pain.
In the pooled analysis, treatment emergent adverse events (TEAEs) were reported by 12.7% of those on AXS-07 and 6.6% on placebo. The most common TEAEs found in AXS-07-treated individuals were nausea, somnolence, and dizziness.
In the original MOMENTUM trial, AXS-07 met its coprimary end points with statistical significance, first showing a greater percentage of patients achieving pain freedom (19.9%) compared with placebo (6.7%; P <.001). Second, the absence of the MBS (36.9%) compared with placebo (24.4%) was significant (P = .002). On secondary end points, AXS-07 showed significant numbers of patients achieving pain-freedom (16.1%) compared with the rizatriptan, MoSEIC meloxicam, and placebo groups, respectively (11.2%, 8.8%, and 5.3%), with all comparisons being significant (P = .038; P = .001; P <.001, respectively).2
In April 2020, months after the initial readout of MOMENTUM, Axsome announced positive results from INTERCEPT. The coprimary end points were also identical to MOMENTUM, with a statistically significantly greater percentage of patients achieving pain freedom compared with placebo (32.6% vs 16.3%, respectively; P = .002) at 2 hours post dose, as well as freedom from the most bothersome symptom (43.9% vs 26.7%, respectively; P = .003).4 AXS-07 also showed efficacy in preventing progression of migraine pain beyond mild intensity and significantly reducing the use of rescue medication, with freedom of pain progression occurring in 73.5% of AXS-07-treated patients compared with 47.4% of placebo patients between 2 and 24 hours post dose (P <.001).3
AXS-07 is currently being assessing in another phase 3 study, EMERGE (NCT05550207), which evaluates efficacy and safety among those with migraine who have experienced an inadequate response to oral CGRP inhibitors. The unique trial, announced in September 2022, will enroll 100 patients who will receive open-label AXS-07 for 8 weeks for at-home treatment of their next 4 migraine attacks. Data from the study will be used to further elucidate the clinical profile of AXS-07 and is not a regulatory requirement.4