Axsome Therapeutics, Inc a clinical-stage biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, announced positive topline clinical trial results from a Phase 1 pharmacokinetic study of AXS-06, a novel, oral, non-opioid, fixed-dose combination of meloxicam and esomeprazole being developed for the treatment of osteoarthritis and rheumatoid arthritis. Axsome has received, from the U.S. Food and Drug Administration (FDA), Pre-Investigational New Drug Application (Pre-IND) written guidance on a proposed clinical developmental plan for AXS-06. Based on this guidance, Axsome believes that AXS-06 is Phase 3-ready. AXS-06 is now Axsome’s third product candidate in clinical development and its second differentiated oral, non-opioid product candidate for the management of chronic pain.
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The clinical trial results demonstrated, for the first time, rapid achievement of peak plasma levels of meloxicam after oral administration. Meloxicam is a long-acting nonsteroidal anti-inflammatory drug (NSAID) with COX-2 preferential inhibition and potent pain relieving efficacy. However standard meloxicam has an extended time to maximum plasma concentration (Tmax) which delays its onset of action. AXS-06 utilizes Axsome’s proprietary MoSEIC™ (Molecular Solubility Enhanced Inclusion Complex) technology to substantially increase the solubility and speed the absorption of meloxicam while maintaining durability of action. AXS-06 also incorporates esomeprazole, a proton pump inhibitor, to reduce the risk of NSAID-associated gastrointestinal ulcers which can occur with chronic NSAID use.
“AXS-06 provides the benefits of oral administration and demonstrates a more rapid meloxicam Tmax than that reported with intramuscular administration, highlighting the potential for faster pain relief. In addition, AXS-06 maintains the long half-life of meloxicam which enables once-daily dosing and sustained effect,” said Herriot Tabuteau, M.D., Chief Executive Officer of Axsome. “These results indicate that AXS-06 has a potentially best-in-class NSAID profile based on the differentiated pharmacokinetic profile of MoSEIC™ meloxicam and the potentially enhanced gastrointestinal safety from the esomeprazole component. The potential efficacy and safety advantages of AXS-06 as compared to currently available NSAIDs could provide significant benefit to patients.”
The study compared the pharmacokinetics of meloxicam and esomeprazole after oral administration of AXS-06 tablets (meloxicam 15 mg, esomeprazole 40 mg), and commercially available Mobic® tablets (15 mg meloxicam) and Nexium® capsules (40 mg esomeprazole) in healthy volunteers. The median Tmax for meloxicam, the trial’s primary endpoint, was 9 times faster for AXS-06 as compared to Mobic® (0.5 hour versus 4.5 hours for AXS-06 and Mobic, respectively, p<0.0001). AXS-06 also demonstrated higher mean maximum plasma concentration (Cmax) (p=0.0018), faster time to therapeutic plasma concentration (p<0.0001), and time to half-maximal plasma concentration (p<0.0001) as compared to Mobic®. Terminal half-lives for meloxicam were similar for AXS-06 and Mobic® at approximately 20 and 22 hours, respectively. Plasma concentrations and terminal half-lives of esomeprazole after AXS-06 and Nexium® administration were comparable. AXS-06 was well tolerated with reported adverse events being similar across the three treatment arms. There were no serious adverse events in the study.
“With its differentiated profile and Phase 3-ready status, AXS-06 complements AXS-02 which is currently in Phase 3 trials in complex regional pain syndrome and knee osteoarthritis,” continued Dr. Tabuteau. “The overlapping patient and physician audiences for AXS-02 and AXS-06 should allow Axsome to leverage our commercialization efforts. We look forward to the further development of AXS-06 and to a data readout for AXS-02 in complex regional pain syndrome anticipated in the fourth quarter.”
Phase 1 Trial Design
The study was a randomized, parallel group trial to evaluate the pharmacokinetics and safety of meloxicam and esomeprazole after single and multiple dose administration of AXS-06 in healthy volunteers. A total of 30 subjects were randomly assigned in a 1:1:1 ratio to treatment with AXS-06 tablets (15 mg meloxicam, 40 mg esomeprazole), Mobic® tablets (15 mg meloxicam), or Nexium® capsules (40 mg esomeprazole), once daily for 6 days under fasting conditions. The primary endpoint was the Tmax of meloxicam. Secondary endpoints included Cmax, time to half maximum concentration, and time to therapeutic concentration.
