|Axsome Therapeutics Announces AXS-02 Independent Data Monitoring Committee Recommends Continuation of COAST-1 Trial and Discontinuation of CREATE-1 Trial|
COAST-1 is a Phase 3 trial of AXS-02 in knee osteoarthritis associated with bone marrow lesions
CREATE-1 is a Phase 3 trial of AXS-02 in complex regional pain syndrome
Significant reduction in bone resorption confirms potent pharmacologic activity
Company to host conference call today at
“We are encouraged by the IDMC’s recommendation for continuation of the COAST-1 trial, by the favorable overall clinical safety profile of AXS-02, and by the confirmation of pharmacologic activity of orally administered AXS-02 as demonstrated by its effects on serum CTx in the CREATE-1 trial,” said Cedric O’Gorman, M.D., Senior Vice President of Clinical Development and Medical Affairs of Axsome. “Knee osteoarthritis associated with bone marrow lesions is a serious and potentially disabling condition with limited treatment options. The demonstrated pharmacologic activity of AXS-02 on bone resorption is relevant not only to knee osteoarthritis but to other potential indications for AXS-02.”
“The outcome of the CREATE-1 interim analysis is disappointing, especially in light of its implication for patients living with complex regional pain syndrome,” said Dr.
In addition to AXS-02, Axsome’s pipeline includes AXS-05, AXS-07, and AXS-06. AXS-05 is a combination of dextromethorphan (an NMDA receptor antagonist, sigma-1 receptor agonist, and serotonin and norepinephrine reuptake inhibitor) and bupropion (a norepinephrine and dopamine reuptake inhibitor, which also increases the bioavailability of dextromethorphan). It is in a Phase 3 trial for treatment resistant depression, a Phase 2/3 trial for agitation associated with Alzheimer’s disease, with a Phase 2 trial in smoking cessation anticipated to be initiated this quarter. AXS-07 is an oral, rapidly absorbed, fixed-dose combination of MoSEIC™ meloxicam and rizatriptan being developed for the acute treatment of migraine, with a Phase 3 trial in this indication anticipated to start this year. AXS-06 is a Phase 3-ready, oral, rapidly absorbed, non-opioid, fixed-dose combination of MoSEIC™ meloxicam and esomeprazole which is being developed for the treatment of osteoarthritis and rheumatoid arthritis and for the reduction of the risk of NSAID-associated gastric ulcers.
The COAST-1 trial is a randomized, double-blind, placebo-controlled, Phase 3 trial in patients with knee OA associated with BMLs. Subjects in the COAST-1 trial are randomized in a 1:1 ratio to receive either AXS-02 or placebo once a week for six weeks. The primary endpoint of the trial is the change in weekly average daily pain intensity, using the 0-10 numerical rating scale, at 24 weeks. The COAST-1 interim analysis included 77 subjects and was conducted to assess the assumptions used to determine the sample size of the study, as well as safety. This study is being conducted pursuant to a
The CREATE-1 trial was a randomized, double-blind, placebo-controlled Phase 3 trial in patients with CRPS. Subjects in the CREATE-1 trial were randomized in a 1:1 ratio to receive either AXS-02 or placebo once a week for six weeks. The primary endpoint of the trial was the change in weekly average daily pain intensity, using the 0-10 numerical rating scale, at 12 weeks. Secondary outcome measures include assessments of the change in the Patients’ Global Impression of Change, Clinicians’ Global Impression of Change, and bone turnover measured using serum carboxy terminal telopeptide of collagen type I (CTx) and serum procollagen type I N terminal propeptide. The CREATE-1 interim analysis included 81 subjects and was conducted to assess efficacy and safety. AXS-02 has received Fast Track designation from the
Conference Call Information
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About Knee Osteoarthritis (OA) associated with Bone Marrow Lesions (BMLs)
Knee OA is a disorder characterized by periarticular bone changes, progressive loss of articular cartilage, joint space narrowing, and eventual total joint failure. It is clinically manifested by knee pain, significant physical disability, and reduced quality of life. BMLs are regions of increased signal intensity on magnetic resonance imaging (MRI) of the knee in patients with knee OA. BMLs are strongly associated with the presence and severity of knee pain, and predict disease severity and structural progression in patients with knee OA, based on published studies. Results of epidemiological studies suggest that there are approximately 7 million symptomatic patients in
About Complex Regional Pain Syndrome (CRPS)
CRPS is a debilitating condition characterized by severe, continuous, burning or throbbing pain in a limb. The excessive pain is accompanied by changes in skin color, temperature and/or swelling. It is considered to be one of the most painful conditions, results in loss of physical function, and can lead to significant and sometimes permanent disability. There is currently no medication approved for the treatment of CRPS.
AXS-02 (disodium zoledronate tetrahydrate) is a potent osteoclast inhibitor being developed as an oral, targeted, non-opioid, potentially first-in-class therapeutic for chronic pain. AXS-02 is dosed once per week for 6 weeks and thereafter may have a duration of effect measured in months. AXS-02 has a high affinity for bone mineral, and reduces osteoclast activity by inhibiting the farnesyl pyrophosphate synthase (FPPS) enzyme. AXS-02 is an investigational product candidate not approved by the
Forward Looking Statements
Certain matters discussed in this press release are “forward-looking statements”. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the success, timing and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation and completion of the trials, futility analyses and receipt of interim results, which are not necessarily indicative of the final results of our ongoing clinical trials; our ability to fund additional clinical trials to continue the advancement of our product candidates; the timing of and our ability to obtain and maintain