AXS-07 effective against migraine pain in phase 3 INTERCEPT trial

Results of the phase 3 INTERCEPT trial showed that AXS-07, an oral agent for acute migraine treatment, was significantly more effective at preventing pain progression than placebo and eliminated migraine pain in approximately one-third of patients within 2 hours of dosing, according to a press release from the manufacturer.

AXS-07 (MoSEIC meloxicam, rizatriptan; Axsome Therapeutics) also substantially relieved patients’ most bothersome symptom compared with placebo, Herriot Tabuteau, MD, CEO of Axsome, reported.

“The percentage of patients achieving migraine pain freedom at 2 hours with AXS-07, which was 33% in this trial, is among the highest reported for any oral agent in recent studies,” Tabuteau said during a webcast presentation. “The percentage of the AXS-07 patients achieving freedom from most bothersome symptom at 2 hours was also substantial at 44%.”

For the 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 mild,” Tabuteau said.

AXS-07 met both coprimary endpoints — freedom from migraine pain (32.6% vs. 16.3%; P = .002) and freedom from most bothersome symptom (43.9% vs. 26.7%; P = .003) after 2 hours of dosing, according to the release. Patients who received AXS-07 were also more likely to achieve sustained freedom from pain up to 24 hours (22.7% vs. 12.6%; P = .03) and 48 hours (20.5% vs. 9.6%; P = .013) after dosing, as well as sustained freedom from pain progression up to 24 hours (73.5% vs. 47.4%; P < .001) after dosing, compared with placebo.

Results further showed that AXS-07 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 (P < .001). More than 73% of patients who received AXS-07 were able to participate in normal activities at 24 hours compared with 47.4% of patients who received placebo (P < .001).

“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,” Stewart J. Tepper, MD, professor of neurology at the Dartmouth-Hitchcock Geisel School of Medicine, said in the release. “As clinicians continue to seek options for their patients with improved efficacy over currently available therapies, AXS-07 may offer an important new treatment for this disabling condition.”

Overall, AXS-07 was safe and well tolerated, according to the release. The most common adverse events included somnolence, dizziness and paresthesia, all of which occurred at a rate of less than 5%. No serious adverse events were reported.

The results of INTERCEPT support previous phase 3 data from the MOMENTUM trial, which showed AXS-07 was effective in a hard-to-treat population with a history of inadequate treatment response, Tabuteau said. In this trial, treatment was only given to patients when their migraine pain was moderate or severe in intensity.

“With the INTERCEPT and MOMENTUM phase 3 trials, AXS-07 has now been evaluated in two positive, well-controlled trials,” Tabuteau said during the webcast presentation. “These studies demonstrate the efficacy of AXS-07 against a both potent active as well as placebo comparators across a spectrum of migraine attack settings, regardless of the timing of migraine treatment, disease severity, prior treatment experience or baseline pain intensity.”

A long-term, open-label trial further evaluating AXS-07 in more than 700 patients is ongoing, he added.

“To date, more than 1,800 patients with migraine have been dosed in our completed and ongoing trials,” Tabuteau said. “We are on track to file a new drug application in the fourth quarter of this year, with the goal of making AXS-07 available to patients as quickly as possible.” – by Stephanie Viguers

Disclosures: Tabuteau is CEO of Axsome. Tepper reports receiving research grants from Alder, Allergan, Amgen, Dr. Reddy’s Laboratories, ElectroCore, Eli Lilly, eNeura, Neurolief, Novartis, Scion Neurostim, Teva and Zosano; consultant and/or advisory board fees from Acorda, Alder, Alexsa, Align Strategies, Allergan, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, Charleston Labs, Decision Resources, DeepBench, ElectroCore, Eli Lilly, eNeura, Equinox, ExpertConnect, GLG, GSK, Guidepoint Global, Healthcare Consultancy Group, Health Science Communications, Impel, Lundbeck, M3 Global Research, Magellan Rx Management, Marcia Berenson Connected Research and Consulting, Medicxi, Navigant Consulting, Neurolief, Nordic BioTech, Novartis, Pfizer, Pulmatrix, Reckner Healthcare, Relevale, Revance, Satsuma, Scion Neurostim, Slingshot Insights, Sorrento, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC and Zosano; salary from Dartmouth-Hitchcock Medical Center and the American Headache Society; stock options from Nocira and Percept; and CME honoraria from the American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital in Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute Peerview, Miller Medical Communications, North American Center for CME, Physicians’ Education Resource, Rockpointe and WebMD/Medscape.