Axsome Therapeutics Announces Primary Endpoint Met in Phase 1 Trial of Next Generation Product Candidate AXS-09 Containing Chirally Pure Esbupropion and Dextromethorphan
Chirally pure and stable single enantiomers of bupropion achieved
AXS-09 consists of esbupropion and dextromethorphan for CNS disorders
Esbupropion is the chirally pure S-enantiomer of bupropion
AXS-09 results in substantial increases in dextromethorphan plasma levels (p<0.0001)
AXS-09 is enabled by Axsome’s technical success at isolating chirally pure and chemically stable single enantiomers of bupropion, and formulating them into dosage forms that maintain their chirality. Enantiomers are molecules which are identical in chemical structure but which differ in the three-dimensional arrangement of the atoms (i.e. mirror images). Based on the results of this Phase 1 trial and preclinical data, Axsome believes that the individual enantiomers of bupropion (R-bupropion and S-bupropion) may each have unique properties that render them potentially useful in different indications. To Axsome’s knowledge, this is the first time that stable, chirally pure single enantiomers of bupropion have been successfully formulated and dosed in a clinical trial.
The increased plasma concentrations of dextromethorphan after dosing with AXS-09, which contains the chirally pure S-enantiomer of bupropion, are comparable to those achieved with dosing of the company’s first generation product candidate AXS-05 (bupropion and dextromethorphan) which contains racemic bupropion (equal amounts of the S- and R-enantiomers). Results of this Phase 1 trial coupled with preclinical data also indicate the potential for enhanced absorption and therapeutic effect of the S-enantiomer as compared to the R-enantiomer.
“We are developing a robust portfolio of novel treatments for CNS disorders, which is an area of high unmet medical needs,” said Cedric O’Gorman, M.D., Senior Vice President, Clinical Development and Medical Affairs of Axsome. “We are actively progressing AXS-05 in our ongoing Phase 3 trial in treatment resistant depression and Phase 2/3 trial in agitation in patients with Alzheimer’s disease, and we look forward to the results of those trials. Based on the positive Phase 1 results, AXS-09 provides us with another attractive product candidate that merits evaluation in future CNS indications.”
“The successful results with AXS-09 reflect Axsome’s continued scientific innovation and are additive to AXS-05 which is already in late-stage clinical trials,” said
AXS-09 is yet another product candidate generated using Axsome’s proprietary medicinal chemistry and formulation technologies which allow the design of new and innovative medicines to treat CNS conditions. These capabilities, which have yielded five clinical-stage product candidates, include: 1) chiral chemistry and formulation to identify, isolate and stabilize chirally pure enantiomers, 2) metabolic inhibition as a novel drug delivery method to increase the bioavailability and prolong the half-life of target drug molecules, 3) the MoSEIC™ technology which is designed to substantially increase the solubility and speed the absorption of target drug molecules, and 4) proprietary chemical synthesis and analysis to increase the solubility and enable the oral delivery of target drug molecules.
Phase 1 Trial Design
The study was a randomized, multiple-dose, parallel group pharmacokinetic trial. A total of 40 healthy adult subjects were randomly assigned to treatment with AXS-09 (esbupropion and dextromethorphan), R-bupropion and dextromethorphan, single-entity S-bupropion, or single-entity R-bupropion tablets, for 8 days under fasting conditions. Plasma concentrations of dextromethorphan, bupropion, and their metabolites were measured. The primary endpoint was the change in dextromethorphan plasma concentrations from day 1 to day 8.
AXS-09 is a novel, oral medicine consisting of chirally pure esbupropion and dextromethorphan being developed for the treatment of central nervous system disorders. Esbupropion is the S-enantiomer of bupropion, a dopamine and norepinephrine reuptake inhibitor and nicotinic acetylcholine receptor antagonist which also serves to increase the bioavailability of dextromethorphan. Dextromethorphan is an NMDA receptor antagonist, sigma-1 receptor agonist, an inhibitor of the serotonin and norepinephrine transporters, and a nicotinic acetylcholine receptor antagonist. AXS-09 is an investigational drug product not approved by the
AXS-05 is a novel, oral medicine under development for the treatment of central nervous system (CNS) disorders. AXS-05 utilizes Axsome’s technology of combining bupropion and dextromethorphan. Dextromethorphan is an NMDA receptor antagonist, sigma-1 receptor agonist, an inhibitor of the serotonin and norepinephrine transporters, and a nicotinic acetylcholine receptor antagonist. Bupropion serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor, and a nicotinic acetylcholine receptor antagonist. AXS-05 is an investigational drug product 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
Source: Axsome Therapeutics, Inc.