An estimated 100 million people suffer from alcohol abuse disorder (AUD) worldwide with health authorities citing the condition as a leading cause of death in young people. But the market for pharmaceutical treatments targeting AUD has been relatively stagnant, and many current options carry significant tolerability issues.

However, after decades of relative standstill, the market for drugs in AUD is on the rise. One of the companies hoping to carve a share in it is Charlottesville, Virginia-based Adial Pharmaceuticals. The company is expecting Phase III data for its pill to treat AUD within the next two months, CEO William Stilley tells Pharmaceutical Technology.

Adial’s pill, called AD04, acts as a serotonin-3 receptor antagonist that could affect neurotransmitters like dopamine and modulate the behavioural effects of alcohol. In a Phase IIb trial, a statistically significant difference of 1.71 drinks/drinking day (p=0.0042) was observed between participants who received AD04 and placebo.

Many of the current treatments available have significant tolerability downsides and are not widely used. Alkermes’ Vivitrol, the current market leader which is also approved for opioid addiction, is administered through multiple injections often associated with adverse events. Disulfiram, which first gained FDA approval to treat alcohol abuse in 1949, works by blocking the body’s ability to break down alcohol, causing severe illness and vomiting upon consuming drinks.

More than 35 million people in the US and 55 million people in Europe have AUD. According to a recent Lancet study, alcohol abuse is the leading cause of death for people in their primes, defined as ages 15 to 49.

But despite the prevalence of AUD, which affects an estimated 100 million people globally, uptake for AUD therapies remains challenging. Many people are unaware they have AUD, and there is often a stigma associated with pursuing any type of treatment, Stilley explains.

By targeting patients genetically with an oral pill, Adial aims to gain traction in a market that could be on the rise, Stilley says. Depression and erectile dysfunction were previously taboo topics, but clinical research and new therapeutic developments have made seeking medication a common and effective treatment, he explains.

According to GlobalData’s consensus sales forecast, the global market for drugs indicated for AUD is expected to more than double between 2022 and 2027, from $2.25 billion to $4.49 billion.

Next steps for Adial

After releasing its upcoming Phase III results, the company plans to seek regulatory guidance on whether it can pursue an accelerated approval or will need to initiate another trial, Stilley says. The regulatory definition of heavy drinking will prove key in Adial’s upcoming Phase III data readout. While the previous Phase IIb trial measured a reduction in drinks per day and frequency of days in which any drinks were consumed, the US FDA requires registrational trials to measure a reduction in heavy drinking days. As such, the Phase III ONWARD trial uses heavy drinking days as its primary endpoint, with secondary endpoints including total alcohol consumption and incidence of adverse events.

In the ONWARD trial, heavy drinking days are defined as more than 60g of alcohol per day for males or 40g alcohol per day for females. In an FDA draft guidance, the agency describes heavy drinking as days with more than four or three standard drinks, for men and women respectively. “The data [indicate that] almost all damage from alcohol abuse comes from this level of heavy drinking,” Stilley says.

If AD04 gains marketing approval, Stilley says its oral formulation could be a key distinguisher among existing alternatives. The current treatment options, including disulfiram, are often “extreme,” and research has shown people with AUD would be more receptive to taking an oral pill, he notes. AD04 is designed as a twice daily pill, but the company plans to study an extended-release formula that would only require one pill a day if AD04 gains marketing approval, Stilley says.