With positive top-line data reported for Axsome Therapeutics Inc.’s oral migraine candidate, AXS-07, in its INTERCEPT trial, the company and the candidate have notched two successful phase III trials in little more than three months.
The INTERCEPT trial hit both co-primary endpoints, freedom from migraine pain and freedom from the most bothersome symptoms as compared to placebo, in early acute treatment. In late December, the phase III MOMENTUM trial hit its co-primary and key secondary endpoints in migraine patients with a history of inadequate response.
The company said ANX-07’s NDA for acute treatment of migraine is still on track for the fourth quarter of this year.
Axsome’s stock (NASDAQ:AXSM) sagged 2.67% to settle at $53.55 per share on April 6. Those shares, however, had plenty of growth momentum already behind them in the past 12 months, having risen from a low of $13.25 nearly a year ago, then dramatically surging in late December to $103.83 when the MOMENTUM top-line data came out.
The migraine space is a crowded one. Biohaven Pharmaceutical Holding Co. Ltd., of New Haven, Conn., gained FDA approval earlier this year for its CGRP receptor antagonist, rimegepant. Data showed rimegepant reduced migraines 4.5 days per month for patients. H. Lundbeck A/S, of Copenhagen, Denmark, has Vyepti (eptinezumab-jjmr), another CGRP receptor antagonist cleared this year for treating chronic migraine. Its phase III study met its primary endpoint of statistically significant reductions in mean monthly migraine days after the first dose over months one to three.
On March 27, Intelgenx Corp. received a complete response letter on its resubmitted 505(b)(2) application for its acute migraine candidate, Rizaport Versafilm, an oral thin-film formulation of the 5-HT1 receptor agonist rizatriptan, the active drug in Maxalt-MLT orally disintegrating tablets, a migraine product marketed by Merck & Co. Inc.
Despite the competition, SVB Leerink’s Marc Goodman wrote Monday that “we remain comfortable that this product can find a niche in the market to drive ~$350M of peak sales.”
In Axsome’s INTERCEPT trial, AXS-07, consisting of Moseic meloxicam and rizatriptan, substantially and significantly eliminated migraine pain, and substantially and significantly prevented progression of migraine pain intensity. It hit both the co-primary endpoints by a statistically significantly greater percentage of patients as compared to placebo achieving pain freedom (32.6% vs. 16.3%, p=0.002) and freedom from patients’ most bothersome symptom (43.9% vs. 26.7%, p=0.003), two hours after dosing. AXS-07 relieved migraine pain, with a statistically significantly greater percentage of patients as compared to placebo achieving sustained pain freedom from two to 24 hours after dosing (22.7% vs. 12.6%, p=0.030), and from two to 48 hours after dosing (20.5% vs. 9.6%, p=0.013). It also eliminated migraine symptoms, with numerical separation from placebo as early as 30 minutes for migraine pain freedom and most bothersome symptom freedom, achieving statistical significance for migraine pain at 90 minutes (p=0.003) and at every timepoint thereafter.
INTERCEPT’s placebo response was higher than that in the MOMENTUM TRIAL. Herriot Tabuteau, Axsome’s founder, chairman, CEO and president, said in Monday’s conference call that “it's along the lines of what one would have expected in this all-comers population. So it is higher than what we're seeing in our MOMENTUM trial. But remember, MOMENTUM was within a very refracted patient population. So their placebo responses were even lower. But this is along the lines of what we would have expected. It's not much greater than what we would have expected.”
H.C. Wainwright analyst Raghuram Selvaraju wrote Monday that while Axsome is on a roll, there are risks in its way, including delays in obtaining clinical data from ongoing mid- and late-stage studies, negative data readouts from ongoing trials, including INTERCEPT, STRIDE-1 and ADVANCE-1 and the inability to secure regulatory approvals for AXS-05, AXS-07, AXS-12, AXS-14 and other pipeline candidates. There is also top-line data from the ADVANCE-1 pivotal trial of AXS-05 in patient agitation associated with Alzheimer’s disease, which could be reported by month’s end.
In addition to the AXS-07 NDA, Axsome is also prepping to file an NDA for AXS-05 in major depressive disorder.