The US Food and Drug Administration (FDA) has agreed to allow ADial Pharmaceuticals to initiate phase III trials of AD04 as a treatment for alcohol use disorder (AUD) in certain targeted genotypes population only. Initially, patients will be screened for the targeted genotypes and only those with one or more of the targeted genotypes will be enrolled in the trial.

Enrolled patients will then be randomized between the active drug and placebo. Performing the phase III trial in only the targeted genotypes significantly reduces the trial size and associated costs and risk of the trial.

"The ability to launch the phase III trials only in subjects having the targeted genotypes represents an important breakthrough for the Company and for this promising new therapy for Alcohol Use Disorder," said William Stilley, chief executive officer, Adial Pharmaceuticals. "Planning is underway to commence phase III trials later this year."

The two endpoints for demonstrating the efficacy of AD04 in the trial are percent of heavy drinking days (PHDD) and the percent of subjects with no heavy drinking days (PSNHDD) in the final two months of the trial. For both endpoints, a heavy drinking day is defined as a day with four or more drinks for women or five or more drinks for men. The European Medicines Authority (EMA) has accepted PHDD as a primary endpoint for approval of drugs for the treatment of alcohol dependence and the FDA has stated that PSNHDD is an acceptable endpoint for demonstrating efficacy of AD04 in the US.

Two successful phase III trials will be required for approval of AD04. Each trial will be 24 weeks in duration and will enroll approximately 600 patients.

According to the National Institute of Alcohol Abuse and Alcoholism (NIAAA), as many as 42 million people in the US alone are afflicted by an alcohol disorder. AUD is characterized by an urge to consume alcohol and an inability to control the levels of consumption. Both acute and chronic consumption of high levels of alcohol are associated with negative social and health consequences.

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. 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.

ADial has patents covering the use of ondansetron in patients with the targeted genotypes for addictions, including alcohol, obesity, and cocaine.

ADial Pharmaceuticals is a privately held pharmaceutical company developing medications for treating addiction diseases and disorders, including alcohol and drug addictions (cocaine, opioids, methamphetamines), as well as other addiction-like behaviors such as those related to obesity and eating disorders.