Date: 2013-04-30
Type of information: Initiation of preclinical development
phase: preclinical data
Announcement: results
Company: Addex Therapeutics (Switzerland)
Product: ADX71441
Action
mechanism: ADX71441 is a GABA-B receptor positive allosteric modulator (PAM) oral small molecule. Oral small molecule GABA-B receptor PAMs have potential in treating multiple indications and Addex has previously demonstrated positive proof of concept in a broad range of preclinical models, including those of pain, anxiety, obsessive-compulsive disorder and overactive bladder (OAB). Addex is positioning ADX71441 as a treatment for spasticity, with multiple sclerosis (MS) being an initial focus of the clinical development program
Disease: alcohol binge drinking
chronic alcohol dependence
Therapeutic area: CNS diseases
Country:
Trial
details: ADX71441, which has potential for once daily dosing and selectively activates the GABA-B receptor, was evaluated in a mouse model of alcohol binge drinking. Acute, oral administration of ADX71441 (3, 10, 30 mg/kg) resulted in a dose-dependent suppression of alcohol intake, achieving 80% reductions at higher doses (10, 30 mg/kg) in comparison to vehicle treatment. Reductions in alcohol consumption in response to ADX71441 treatment were present for the entire 4hour alcohol access period. The effect of ADX71441 in this model was more robust and longer-lasting than that seen in mice treated with naltrexone, which was used in the study as a positive control. This is the first study showing efficacy of a GABA-B receptor PAM in a rodent model of alcohol binge drinking. The compound was also evaluated in an intermittent access to alcohol model of chronic alcohol dependence in mice.
Latest
news: * On April 30,2013, Addex, a company pioneering allosteric modulation-based drug discovery and development, has announced preclinical data for its GABAB receptor positive allosteric modulator (PAM) oral small molecule in a validated rodent model of chronic alcohol dependence. ADX71441 demonstrated robust and dose-dependent suppression of alcohol intake in animals lasting 24 hours. The compound was evaluated in an intermittent access to alcohol model of chronic alcohol dependence in mice. This procedure generates excessive voluntary alcohol drinking after animals are given 24-hour access to alcohol concomitant to water every other day. In animals with a history of 4 weeks of excessive drinking, oral ADX71441 (3, 10, 17 mg/kg), administered acutely, resulted in a dose-dependent suppression of alcohol intake, achieving 70% reductions at the higher doses (17 mg/kg) in comparison to vehicle treatment. Significant reductions in alcohol consumption in response to ADX71441 treatment were present for the entire 24-hour alcohol access period. The effect of ADX71441 in this model was more robust and longer-lasting than that seen in mice treated with naltrexone, used in the study as a positive control. Also, the effect of ADX71441 was characterized with remarkable behavioral specificity since water consumption was not influenced by the treatment.
Based on ADX71441 current data package, Addex is positioning the drug candidate as a treatment for the rare disease CMT1a, a form of peripheral neuropathy as well as for patients with spasticity, e.g. in multiple sclerosis or spinal cord injury. Addex now looks forward to initiate clinical testing for ADX71441 by July 2013. The company expects to deliver top-line safety, pharmacokinetic and biomarker data on ADX71441 by year end.
* On October 29, 2012, Addex Therapeutics has announced positive preclinical data for its GABA-B receptor positive allosteric modulator (PAM) oral small molecule, ADX71441, in a validated rodent model of alcohol binge drinking. ADX71441 demonstrated robust, dose-dependent and long-lasting suppression of alcohol intake in animals compared to naltrexone, the most-commonly prescribed treatment of alcoholism on the market. "These data are extremely encouraging and superior to naltrexone in our pre-clinical model, and warrant further exploration as a novel treatment for alcoholism,\" said Professor Klaus Miczek at Tufts University (USA) in whose laboratory the study was performed.
Both clinical and pre-clinical data suggest that activation of the GABA-B receptor offers a unique therapeutic opportunity to address largely unmet needs of patients with alcohol and drug abuse by
(1) reducing the alcohol or drug intake;
(2) alleviating many physical signs (pain, Gastrointestinal/urinary disturbances) and emotional symptoms (anxiety) associated with withdrawal;
(3) maintaining abstinence by reducing alcohol or drug craving.
Addex Therapeutics is now looking forward to the filing of a CTA for ADX71441 by the end of 2012 and initiating Phase 1 testing in Q1 2013.
