➤Adial Pharmaceuticals Inc. is developing a serotonin blocker drug for alcohol use disorder, or AUD, which currently has limited therapeutic options.
➤According to Adial CEO William Stilley, existing treatments including disulfiram, acamprosate and Alkermes PLC's Vivitrol, or naltrexone, are extreme.
Charlottesville, Va.-based Adial completed an IPO in July 2018. Its AUD therapy, currently called AD04, will enroll two consecutive phase 3 trials in Europe and the U.S., with data expected by the end of 2020.
This interview has been condensed for clarity.
S&P Global Market Intelligence: Treatment with AD04 is preceded by a genetic test. How does it work and what is it targeting?
Adial Pharmaceuticals president
William Stilley: What this genetic test does is identify those with whom the drug would be expected to work. If you're positive you get the drug, and if you're not positive, the drug wouldn't be expected to work. There's nothing special about the test; it's a standard polymerase chain reaction test. But knowing which genes to look at is critical, and that's the newness of it. We believe right now there are 14 different serotonin receptors and receptor cell types, and we target just one of those with a serotonin 3 blocker. So AD04 blocks serotonin 3, which works upstream of the dopamine system.
The genetic test is a companion diagnostic, and it would be approved at the same time as AD04.
What were the endpoints of the phase 2b trial?
The primary endpoint was severity of drinking, which is, on the days you drink, how much you drink. The secondary endpoint was frequency of drinking measured by percentage of days abstinent, when you haven't had drinks. What happened in our 283-patient trial is that patients who were on the drug of genotype had a dramatic and significant decrease in frequency of drinking, so they drank almost half as often, and when they drank they drank about 60% less.
I'd also say, there's this whole idea, abstinence versus what they call reduction of harm, which is reduction of drinking, and both the European Medicines Agency and the U.S. Food and Drug Administration agreed that heavy drinking days are the culprit. It's like a linear curve: the more heavy drinking days you have in a month, the worse the outcomes. There are over 200 diseases caused by alcohol. You reduce alcohol consumption, you reduce bad outcomes, you reduce costs.
How was data reported?
It's self-reported; they came in every week. And there's been a lot of work trying to figure out the best ways to report, and [Adial chairman] Bankole Johnson found out that the best way you can get the answer is, you have to remove the person from the alcohol, remove the person from the day and ask them to report back what happened. If you're in a study, you don't really have an incentive to cheat. And if there is any, it's going to be the same between drug and placebo.
If you ask, last Monday, did you drink? That's very objective, that's an event. So there's no subjectivity, only memory problems, which is very different from a lot of diseases where you're measuring subjectivity. And then you ask, how much did you drink, and then you take them to a table and there's a variety of glasses, bottles, and you ask what kind of glass. Then you ask how far was it filled and what were you drinking, and then pour it into a bucket and measure it. And both the EMA and FDA consider that a validated collection method.
What have been the challenges of developing an AUD treatment?
You have to meet the need. If you think about another addiction, in nicotine, they had all sorts of treatments for many decades — Nicorette, cessation programs. It wasn't until a simple, oral drug that actually reduced craving for nicotine came out, called Chantix, that overnight it was a billion-dollar drug. Those other things didn't really stop the craving, they had side effects, they were life makeovers, which is really extreme treatment.
The treatments today for alcohol are extreme. Alcoholics Anonymous will even tell you: You will likely not be willing to tolerate the treatment we want you to undergo unless you've hit "rock bottom," meaning your life has been destroyed.
So then if you want to take one of the pharmacologic answers, like Antabuse (or disulfiram), which has been on the market for decades, you take the pill, then you drink, get violently ill — throw up all over the place, which can be fatal, actually. The other market leader today is Vivitrol. So every 30 days you have to go in for an 18-gauge needle; they give you one of the most painful injections known and put a huge chunk of gel into your backside. So those are your options.
We have a simple, easy-to-use pill that does the job it's supposed to do, you take in the confidence of your doctor and it's genetically targeted for you.