The investigational acute migraine drug AXS-07 met both of its co-primary endpoints in patients who had inadequate response to prior treatment, the phase III study showed.
The dual-mechanism treatment -- a combination of meloxicam, a nonsteroidal anti-inflammatory drug (NSAID), and rizatriptan, a 5-HT1B/1D agonist -- bested placebo on 2-hour pain freedom and 2-hour freedom of most bothersome symptom, reported Richard Lipton, MD, of the Montefiore Headache Center at Albert Einstein College of Medicine in New York City, and co-authors.
AXS-07 also showed superiority to an active comparator, they said in an of late-breaking research from the American Academy of Neurology , a platform for research from the AAN annual meeting, which was cancelled due to the COVID-19 pandemic.
"There is a scientific basis for believing that triptan-NSAID combinations should work well in combination for the treatment of migraine," Lipton told 鶹ý. "Triptans target trigeminal nerve endings to block the release of calcitonin gene-related peptide. The treatment has advantages in people who do not respond to a single mechanism."
AXS-07 uses a proprietary technology called (Molecular Solubility Enhanced Inclusion Complex), developed by Axsome Therapeutics. The technology is designed to increase meloxicam's solubility and speed of absorption after the drug is taken orally while maintaining its extended plasma half-life.
MOMENTUM was a randomized, double-blind, multicenter, single-dose trial of 1,594 migraine patients. Qualifying participants had a history of inadequate response to prior migraine treatments, identified by a score of 7 or less on the (mTOQ-4). Patients with a history of significant cardiovascular diseases or uncontrolled hypertension were excluded.
Researchers randomized patients 2:2:2:1 to one of four groups: AXS-07 (20 mg MoSEIC meloxicam/10 mg rizatriptan), rizatriptan (10 mg), MoSEIC meloxicam (20 mg), or placebo. "The design allowed us to test whether the combination was better than its ingredients in a manner required by scientific rigor and FDA guidance," Lipton said.
Patients in all four groups had a mean age of 41, and 81% to 85% were female. At baseline, participants had an average total mTOQ-4 score of 3.5 to 3.9, indicating poor response to earlier treatment. Across the groups, 35% to 40% had previously used triptans.
A greater percentage of patients achieved pain freedom in 2 hours with AXS-07 than placebo (19.9% vs 6.7%; P<0.001, with a placebo corrected difference of 13%). AXS-07 also showed superiority over placebo on freedom from most bothersome symptom (photophobia) at 2 hours (36.9% vs 24.4%; P=0.002, with a placebo corrected difference of 13%).
"The low placebo response for pain freedom at 2 hours (6.7%) is reflective of the difficult-to-treat patient population the study sought to enroll," the researchers noted.
Compared with rizatriptan, meloxicam, and placebo, AXS-07 showed greater numbers of patients achieving pain freedom. A time course analysis showed that AXS-07 achieved statistical significance over rizatriptan at 60 minutes (P=0.04).
Rescue medication was used by 23% of patients treated with AXS-07, 34.7% of rizatriptan users, 35.1% of MoSEIC meloxicam users, and 43.5% of placebo users (P<0.001 for each group vs AXS-07).
AXS-07 appeared to be well tolerated. Treatment-emergent adverse events occurred in 11.1% of patients treated with AXS-07, mostly nausea (2.7%), dizziness (1.6%), and somnolence (1.4%). Adverse events occurred in 15.4% of the rizatriptan group and 11.5% of the meloxicam group, with nausea mentioned most frequently.
"The combination product was better than placebo, and better than rizatriptan alone and better than meloxicam alone," Lipton noted. "There have been few studies of acute treatments for migraine that have evaluated combinations of prescription drugs."
In April, Axsome announced that AXS-07 also met its co-primary endpoints in the phase III trial of early migraine treatment. The company plans to file a for AXS-07 with the FDA in the fourth quarter of this year.
Disclosures
The study was supported by Axsome Therapeutics.
Lipton developed the mTOQ and has received consulting fees from Axsome, but has no financial interest in the company. Several co-authors were employees of Axsome Therapeutics.
Primary Source
American Academy of Neurology
Jones A, et al "Efficacy and Safety of AXS-07 for the Acute Treatment of Migraine: Results from the MOMENTUM (Maximizing Outcomes in Treating Acute Migraine) Phase 3 Randomized, Double-blind, Active- and Placebo-Controlled Study" AAN Science Highlights 2020, presentation 46996.