Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.
AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.
“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.
The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.
Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
Uncertain therapeutic advantage
Commenting on the findings,, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.
“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.
It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.
In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.
For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.
Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07). The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.
“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.
“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.
The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.
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