A year after it became the first technology company spun out of University of Virginia research to offer an initial public stock offering, Adial Pharmaceuticals is set to test its anti-alcohol abuse drug on 290 Europeans.
Last summer, the Albemarle County-based company went public with a $7.32 million stock issue, the proceeds from which will be used to fund research.
The company’s product, labeled AD04, is designed to reduce alcohol cravings as a way to effectively curb alcohol intake in people who have a genetic predisposition to alcohol use disorder. The newest trials will take place in Europe because, although the problem affects people everywhere, studies show that genetic predisposition is greater in northern and eastern Europeans.
“Everyone has a story, whether it’s a family member, a friend, a business partner or a parent — alcohol use disorder is so prevalent that it touches everybody,” said William Stilley, Adial’s CEO and president.
“Think about it. This is a problem so bad that the United States actually changed its Constitution to make alcohol illegal as a way to try and fix it, and it still didn’t work. They had to change it back,” Stilley said. “People don’t talk about it much anymore because what can you say about alcohol abuse that hasn’t been said in the last 80 years.”
From jogging, to yoga to getting drunk, Stilley said people are driven to do things by two motivators — desire and fear. With alcohol and other drugs, that can be problematic.
“People often get into addiction because of desire. They desire the feeling that they get or the social atmosphere that goes with it,” he said. “But for some, they wind up not doing it for the desire or for the joy, but the fear of not having it.”
Addicts may fear going through detoxification or not having access to a substance. That can create panic and lead to thievery, violent disagreements and other problems.
“They would rather do whatever it is they believe they need to do — steal or prostitution, for instance — to get it because they see themselves going through a living hell if they don’t have it,” Stilley said.
According to the National Institutes of Health, current drug treatments for alcohol use disorder are designed to work with behavior modification to support major changes in behavior or environment for those with the disorder.
Disulfiram, also called Antabuse, causes negative physical effects if alcohol is consumed. Naltrexone tempers the pleasurable effects of alcohol. Acamprosate, also called Campral, works to keep neurochemical systems in the brain at normal levels.
Adial’s once-a-day pill reacts with serotonin receptors that create cravings for alcohol and the euphoric feelings that result from satisfying those cravings. It can be targeted to individuals through genetic testing to determine if they have genes that make them susceptible to alcohol abuse.
“In alcohol use disorder, there is clearly a genetic component that goes across all races and there is also and environmental component,” Stilley said. “Alcohol has been used by humans in all cultures throughout history — and so has the disorder.”
Adial has contracted with Crown CRO, a Finnish firm, to conduct the phase-three testing. Five sites in Europe have been chosen for the testing.
“Over 55 million people are afflicted with this disease in Europe alone,” said Crown CEO Tarja Leikas. “Given the prevalence of alcohol use disorder and the targeted genotype for AD04, we expect to be able to leverage our geographic expertise, especially within Scandinavia and Eastern Europe, to rapidly enroll patients while effectively managing costs.”
The U.S. Food and Drug Administration requires new drugs to go through a three-phase study process. The first phase is animal testing, which is designed to show whether a drug is effective and if it is likely safe for humans.
The second phase is designed to see if the drug reacts in humans as it did it in animals.
“You’re trying to learn how it works in humans, if it works at all and what the safety markers are,” Stilley said.
ADO4 proved successful in its second-phase trial for those who have the genetic markers for the disorder by helping to decrease the frequency of alcohol use, the number of drinks taken and the number of days during which the test groups drank heavily.
According to the Centers for Disease Control and Prevention, moderate drinking is one drink per day for women and two drinks per day for men. Heavy drinking is defined as 15 or more drinks per week for men and eight or more drinks per week for women.
Binge drinking is considered five or more drinks in two to three hours by men and four or more drinks in two to three hours by women.
The totals are different for men and women because their bodies process alcohol differently, including the amount of time it takes for their bodies to clear it out of their system and in the way alcohol impacts their organs.
After the second phase showed no overt safety concerns for human use of AD04, the FDA approved the drug for phase-three testing.
“Phase three is where you try to prove what you think you know and compare them against placebos to make sure that they are effective,” Stilley said. “You’re dealing with a wide group of patients so you get more safety information.”
Stilley said that if AD04 eventually is approved by the FDA, the company intends to investigate the drug’s ability to ease opioid and other addictions.
“We all have things we are addicted to, like oxygen and food. But for some addicts, they have something that their body desires even more than food,” he said. “That’s where our research comes in. Our goal is to have a company that is focusing on addiction and ways to treat it.”