AD04 is being developed as a treatment for alcohol use disorder in patients of select genotypes. AD04 is a serotonin-3 (5HT3) antagonist that is believed to interrupt the reinforcing effects of alcohol, and thus reduces the urge to drink. Such reinforcing effects are thought to be exaggerated in patients that have certain mutations of the genes that control serotonin function in the brain, and these are the patients targeted for treatment with AD04. ADo4 represents a paradigm shift for treating alcohol addiction because it does not require total abstinence but allows patients to better control their drinking and reduce their heavy drinking.
AD04 contains an ultra-low dose of the active ingredient ondansetron, which is currently marketed as an anti-emetic for post-operative and post-chemotherapy nausea. Doses effective for treating alcohol addiction are well below those used to treat emesis. Clinical and non-clinical experience to date suggest that higher doses like those used for the treatment of emesis may have reduced efficacy for treating addiction and additional safety risks associated with their chronic use as would be required for treatment of addiction.
In a 283-person Phase IIb trial, AD04 showed significance in both primary endpoints by increasing the percentage of days of abstinence and decreasing the drinks per drinking days in patients of the targeted genotypes as compared to both the placebo groups and patients on drug of the other genotypes. Significance was also achieved in reducing the percentage of heavy drinking days. Reported drug related side effects in the trial were limited.
AD04 is hypothesized as a potential treatment for other addiction diseases such as obesity, illegal drug use, and smoking. Phase II studies in other addictions may be conducted in the future.