Addiction is a common disease and likely everyone knows someone who has struggled with it in some way.
Alcohol use disorder is one of the most common addictions globally, affecting nearly 400 million people. That is 7% of the world’s population aged 15 and above, according to the World Health Organization’s global status report on alcohol and health and treatment of substance use disorders.
“Alcohol use disorder is a large public health need in the world,” said Cary Claiborne, CEO of Adial Pharmaceuticals, adding that “very few people actually seek any kind of treatment, and most don’t seek medical treatment.”
Psychosocial interventions are often used to treat AUD, with the objective of reducing intake, achieving abstinence, and preventing relapses. There are also pharmacological treatments, but most of them require the patient to be abstinent to start medication.
In over 15 years, there have not been any new treatments in the US, where it is estimated that AUD affects over 30 million people, Claiborne told Generics Bulletin in an exclusive interview.
And that is the issue Adial is trying to solve. The clinical-stage biopharma company is preparing for the last development stage for its lead asset AD-04, a repurposed version of antiemetic drug ondansetron.
Filling The Gap With A Non-Abstinence-Based Approach
Ondansetron was first approved by the US Food and Drug Administration in 1991 under the name Zofran to alleviate nausea and vomiting in patients who received chemotherapy.
The drug blocks the serotonin-3 receptor, which impacts the dopamine reward system. As such, AD-04, which is a near-micro dose of ondansetron, lowers the cravings and the impulse to drink in patients with certain genetic biomarkers, explained Claiborne.
“That’s a key driver in trying to treat addiction. A lot of addictions are associated with cravings and impulses, and alcohol use disorder is definitely prone to that,” he added.
Adial is also taking a different approach to treating addiction. AD-04 aims to moderate and reduce alcohol intake in a non-abstinence-based approach.
Other drugs require the patient to stop drinking alcohol entirely before starting the treatment. These include medication such as naltrexone, commonly used as a first-line therapy for AUD, and Antabuse (disulfiram), which acts as a deterrent by producing unpleasant side effects if alcohol is consumed.
“We feel like all the drugs have some shortcomings and we believe our drug fills that need. Probably the largest one is the fact that you don’t have to be abstinent to start our treatment,” Claiborne said.
Focusing On Specific Genotype After Failed Phase III
Adial recently reported positive data from a pharmacokinetics trial with healthy volunteers, showing predictable bioavailability relative to the reference drug. Now, the firm is preparing for a meeting with the FDA to discuss the upcoming Phase III program, to get the drug across the line to the market.
However, this is not the first Phase III trial for AD-04. Back in 2022, the drug failed to meet the primary endpoint of change from baseline in the monthly number of heavy drinking days during the last eight weeks of the 24-week treatment period.
The trial had two groups, heavy and very heavy drinkers. While the first cohort showed a statistically meaningful 79% reduction in drinking, the outcome was skewed by the high placebo response among very heavy drinkers, defined as individuals who average 10 drinks per drinking day.
Still, in a post hoc analysis, Adial identified a subgroup of patients with a specific genotype that did better than others. This population will be the focus of the upcoming studies, which may include one or two Phase III trials.
Looking For Commercial Partners
Claiborne hopes to conduct these two trials in parallel or in short order, with the goal of filing for registration and launching AD-04 in 2027.
The US is the primary market for Adial, but it also collects data that could support European registration, especially as the previous Phase III trial was conducted in Central and Eastern Europe, as well as Scandinavian countries.
To bring AD-04 to the market, Adial wants to have a partner, both in the US and Europe, or other markets if opportunities arise. While the firm could go solo as several of its staff have been on the commercial side in other larger companies, Claiborne said that it is not their plan at this point.
“It is more efficient and better for our shareholders to partner with a company that already has commercial infrastructure in the addiction space or adjacent space where they could launch the drug,” he explained.
When partnered, Adial would look at what else it could do with AD-04, either with additional indications or label expansions, or bringing in additional assets in the addiction space to fill out its portfolio.
The CEO said that the drug could be used to treat opiate use disorder, and the firm has some patents tied to this indication. But, given the company size, Adial is focused on the current program.
“We’re always open to other potential opportunities that may come our way to look at, but given where we are right now, our focus is on AD-04 moving it for alcohol use disorder,” he added.
Opening The Door For Discussing Treatment
Adial’s current intellectual property protection lasts until 2031, but it filed a new patent to protect core assets last summer. If granted, it could extend IP exclusivity on core technology to 2044.
Most recently, the US Patent and Trademark Office issued a new patent covering methods of identifying patients with certain genetic markers linked to substance use disorders, specifically the TT genotype of rs1042173 in the serotonin transporter gene.
The diagnostic genetic test is partnered with Boudicca Dx after the duo signed an agreement last August. The precision medicine testing firm is supporting Adial in advancing its technical and regulatory strategy for the genetic test, which will be used to recruit for the upcoming Phase III program.
“My mission is to get this drug to market where we can start helping the millions of patients that are suffering from this terrible disease."
AD-04’s launch into the market will be accompanied by the diagnostic genetic test, which will be carried out by physicians. This will not only identify people with specific biomarkers but could also increase the likelihood of patients considering treatment altogether.
“It opens the door to a discussion where [physicians] can say, there’s a test that we can give you and, if you test positive for the biomarker we’re looking for, we have a drug that may be able to help you drink less,” the CEO explained, adding that it would give patients a reason to think about why they struggle with alcohol in the first place.
Claiborne, who previously held a CFO position at Indivior, a pharma company developing treatments for opioid use disorder, has seen the impact addiction can have on families. “Everyone I’ve talked to knows someone or knows of someone that suffered in some way from opiate use disorder or alcohol use disorder,” he said.
Adial has a clear plan over the next several years on how to bring AD-04 into the market and how to break the one-size-fits-all approach in treating addiction.
“My mission is to get this drug to market where we can start helping the millions of patients that are suffering from this terrible disease,” Claiborne aspired.
