Axsome Therapeutics Announces AXS-07 Achieves Both Co-Primary Endpoints and Prevents Migraine Pain Progression in the INTERCEPT Phase 3 Trial in the Early Treatment of Migraine
Achieved freedom from migraine pain in 33% of AXS-07 patients versus 16% for placebo at 2 hours (co-primary endpoint, p=0.002)
Prevented progression of migraine pain beyond mild intensity in 74% of AXS-07 patients versus 47% for placebo from 2 to 24 hours (p<0.001)
Return to normal functioning achieved in 74% of AXS-07 patients versus 47% for placebo at 24 hours (p<0.001)
Significantly reduced rescue medication use, with 15% of AXS-07 patients using rescue versus 42% of placebo over 24 hours (p<0.001)
Achieved freedom from most bothersome symptom in 44% of AXS-07 patients versus 27% for placebo at 2 hours (co-primary endpoint, p=0.003)
Rapidly relieved migraine symptoms with numerical superiority starting 30 minutes after dosing
NDA submission of AXS-07 in the acute treatment of migraine on track for 4Q 2020
Company to host conference call today at
AXS-07 met both of the two co-primary endpoints by demonstrating a statistically significantly greater percentage of patients as compared to placebo achieving pain freedom (32.6% versus 16.3%, p=0.002) and freedom from most bothersome symptom (43.9% versus 26.7%, p=0.003), 2 hours after dosing. AXS-07 durably relieved migraine pain with a statistically significantly greater percentage of patients as compared to placebo achieving sustained pain freedom from 2 to 24 hours after dosing (22.7% versus 12.6%, p=0.030), and from 2 to 48 hours after dosing (20.5% versus 9.6%, p=0.013). AXS-07 rapidly 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.
A single dose of AXS-07 significantly prevented progression of migraine pain beyond mild intensity while significantly reducing the use of rescue medication. Freedom from pain progression from 2 to 24 hours after dosing was achieved by 73.5% of AXS-07 patients versus 47.4% of placebo patients (p<0.001). The effect on pain progression translated to a significant reduction in the use of rescue medication, with only 15.3% of AXS-07 patients requiring rescue medication through 24 hours after dosing, versus 42.2% of placebo patients (p<0.001).
AXS-07 substantially and significantly reduced functional disability, and demonstrated overall disease improvement. AXS-07 treatment resulted in 73.5% of patients able to perform normal activities at 24 hours compared to 47.4% of placebo patients (p<0.001). On the Patient Global Impression of Change (PGI-C) scale, 52.4% of AXS-07 patients were very much or much improved compared to 27.7% of placebo patients (p<0.001).
“The INTERCEPT study demonstrated high rates of freedom from migraine pain with AXS-07 treatment, and utilized an innovative design to evaluate migraine pain progression. It is remarkable that early treatment with AXS-07 prevented migraine pain progression in the vast majority of patients and enabled a similarly high percentage of patients to return to normal functioning,” said Dr.
AXS-07 was generally safe and well tolerated in the trial. The most commonly reported adverse events with AXS-07 were somnolence, dizziness, and paresthesia, all of which occurred at a rate of less than five percent. There were no serious adverse events in the trial.
“We are very pleased with the strong results of the Phase 3 INTERCEPT trial, which confirm the superior and durable efficacy of AXS-07. The prevention of migraine pain progression, and the substantial increase in the rate of pain freedom demonstrated with early treatment with AXS-07, expand and enhance its differentiated profile for the acute treatment of migraine,” said
AXS-07 has been evaluated in the completed MOMENTUM Phase 3 trial for which positive results were previously announced. The MOMENTUM trial enrolled only patients with a history of inadequate response to prior acute treatments, with patients waiting to treat their attacks only when the migraine pain had reached moderate or severe intensity. This is in contrast to the INTERCEPT trial, which enrolled all comers and in which patients were instructed to administer AXS-07 at the earliest sign of migraine pain while the pain was mild, before progressing to moderate or severe intensity.
“Migraine is one of the most disabling disorders, incapacitating sufferers and seriously damaging home life, social activity and the ability to work. Published surveys have underscored that patients remain dissatisfied with the efficacy of currently available therapies,” said Cedric O’Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs of Axsome. “The results of the INTERCEPT trial demonstrate for the first time that AXS-07 can halt migraine pain progression before reaching moderate or severe intensity. These data grow the body of clinical evidence in support of the potential of AXS-07 to be a multi-mechanistic treatment for migraine with efficacy that is superior to the current standard of care, and which can rapidly, robustly, and durably alleviate symptoms, and return patients to their normal daily activities.”
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 neuro-inflammation, 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. AXS-07 is covered by more than 30 issued
Detailed study results, including additional secondary endpoints, will be submitted for presentation at upcoming medical meetings and for publication.
Summary of Topline Results of the INTERCEPT Trial
Patient Population
- Patients were instructed to administer AXS-07 at the earliest sign of migraine pain, while the pain was mild, before progressing to moderate or severe intensity.
- Enrolled all comers.
Co-Primary Endpoints, Onset, and Durability
- AXS-07 demonstrated statistically significant improvement as compared to placebo on both of the co-primary endpoints of pain freedom (32.6% versus 16.3%, p=0.002), and freedom from most bothersome symptom (43.9% versus 26.7%, p=0.003), 2 hours after dosing.
- AXS-07 was numerically superior to placebo as early as 30 minutes for migraine pain freedom and most bothersome symptom freedom, achieving statistical significance for migraine pain freedom at 90 minutes (p=0.003) and at every time thereafter.
- Sustained pain freedom from 2 to 24 hours after dosing was experienced by 22.7% of patients treated with AXS-07, compared to 12.6% with placebo (p=0.030).
- Sustained pain freedom from 2 to 48 hours after dosing was experienced by 20.5% of patients treated with AXS-07, compared to 9.6% with placebo (p=0.013).
Prevention of Migraine Pain Progression, and Rescue Medication Use
- AXS-07 prevented progression of migraine pain intensity beyond mild in 73.5% of patients versus 47.4% of placebo patients from 2 to 24 hours (p<0.001).
- Rescue medication was used by 15.3% of AXS-07 patients, compared to 42.2% of placebo over 24 hours (p<0.001).
Functional and Global Improvement
- The ability to perform normal activities was achieved by 73.5% of AXS-07 patients compared to 47.4% of placebo patients at 24 hours (p<0.001).
- On the Patient Global Impression of Change (PGI-C) scale, 52.4% of AXS-07 patients were very much or much improved compared to 27.7% of placebo patients (p<0.001).
Safety and Tolerability
- AXS-07 was generally safe and well tolerated in the trial.
- The most commonly reported adverse events with AXS-07 were somnolence, dizziness, and paresthesia, all of which occurred at a rate of less than five percent.
- There were no serious adverse events in the trial.
Conference Call Information
Axsome will host a conference call and webcast with slides today at
About the INTERCEPT Trial
INTERCEPT (Initiating Early Control of Migraine Pain and Associated Symptoms) is a Phase 3, randomized, double-blind, multicenter, placebo-controlled trial evaluating the early treatment of migraine with AXS-07. A total of 302 patients were randomized in a 1:1 ratio to treatment with AXS-07 or placebo. Patients were instructed to administer AXS-07 at the earliest sign of migraine pain, while the pain was mild. The two co-primary endpoints of the trial are the proportion of patients who are free from headache pain two hours after dosing, and the proportion of patients who no longer suffer from their most bothersome migraine-associated symptom (nausea, photophobia, or phonophobia) two hours after dosing.
About Migraine
Over 37 million Americans suffer from migraine according to the
About AXS-07
AXS-07 is a novel, oral, investigational medicine with distinct dual mechanisms of action under development for the acute treatment of migraine. AXS-07 consists of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (
About
References
- Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in
the United States : A summary report and call to action. Ann Neurol. 2017 Apr; 81(4):479-484. - Smelt AF, Louter MA, Kies DA, Blom JW, Terwindt GM, van der Heijden GJ, De Gucht V, Ferrari MD, Assendelft WJ. What do patients consider to be the most important outcomes for effectiveness studies on migraine treatment? Results of a Delphi study. PLoS One. 2014 Jun 16;9(6):e98933.
- Lipton RB, Stewart WF. Acute migraine therapy: do doctors understand what patients with migraine want from therapy? Headache. 1999;39(suppl 2):S20-S26.
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Source: Axsome Therapeutics, Inc.