by Randolph W. Evans, MD

People with migraine desire a tolerable acute medication which quickly relieves the pain without recurrence. Rizatriptan is a fast acting oral triptan. In a meta-analysis, rizatriptan 2 hour pain relief was 71% vs 38% for placebo.  However, only 37% had sustained pain relief. We have been combining triptans with NSAIDS for several decades to reduce recurrence.

Meloxicam is a COX-2 selective NSAID with a half-life of about 15-22 hours which is advantageous for sustained pain relief and freedom. In acutely treating migraine, meloxicam inhibits cyclooxygenaase and PGE2 and reverses central sensitization while rizatriptan inhibits the relase of CGRP and CGRP-mediated vasodilation as well as decreasing pain signals to the trigeminal nucleus caudalis.

In this study, the molecular solubility enhanced inclusion technology or MoSEIC technology developed by Axsome was used which is a patented buffered drug-carrier complex combined with a pH modifier which significantly improves the rate and degree of drug absorption. MoSEIC meloxicam has a Tmax of 15 minutes with a maintained half-life of approximately 20 hours.

O'Gorman and colleagues enrolled patients with a history of inadequate treatment response to prior acute migraine treatments and high rates of characteristics strongly associated with poor treatment outcomes including cutaneous allodynia (75.4%), severe migraine pain intensity (41.2%), obesity (43.7%), and morning migraine (36.6%).  A total of 1,594 patients were randomized in a 2:2:2:1 ratio to AXS-07 (20 mg MoSEIC™ meloxicam/10 mg rizatriptan), rizatriptan (10 mg), MoSEIC™ meloxicam (20 mg), or placebo, to treat a single migraine attack of moderate or severe intensity. Treatment with AXS-07 resulted in rapid, sustained, substantial, and statistically significant efficacy as compared to placebo, rizatripan, and a a highly effective and rapidly-acting active comparator, in the acute treatment of migraine in patients with a history of inadequate response to prior acute treatments. 

AXS-07 reminds me of Reece's candy where you combine chocolate and peanut butter and create something new. Here you combine rizatriptan with MoSEIC meloxicam which has impressive efficacy in difficult to treat migraine patients. It is not known whether this formulation is superior to Treximet without a comparator study.

 

References:

1. Ferrari MD, Loder E, McCarroll KA, Lines CR. Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials. Cephalalgia. 2001;21(2):129-136
2. MoSEIC Technoogy. Axsome Therapeutics. Available at https://axsome.com/science/moseic-technology/
3. Law S, Derry S, Moore RA. Sumatriptan plus naproxen for the treatment of acute migraine attacks in adults. Cochrane Database Syst Rev 2016; 4:CD008541.