Topline results for ONWARD phase III trial for AD 04 in patients with alcohol use disorder

AD 04 achieved statistically significant mean reduction in heavy drinking days among the pre-specified group of “heavy drinkers” (defined below). AD 04 also showed safety and tolerability that compared favorably to placebo. Adial intends to share the results of the ONWARD trial with the relevant health authorities to discuss the appropriate next steps towards the expeditious development of AD 04 and to seek product approval.

Highlights of topline ONWARD data: i. AD 04 patients, compared with placebo patients, achieved a statistically significant reduction from baseline at month six in heavy drinking days for the pre-specified patient group of heavy drinkers (avg. <10 drinks per drinking day at baseline; p="0.03)," which accounted for approximately two-thirds of the trial population. a similar trend was seen in the combined month five and six analysis in the reduction from baseline (p="0.07)." notably, in the last month of the trial, ad 04 heavy drinking patients had a mean reduction of approximately 79% in heavy drinking compared with baseline. ii.ad 04 patients, compared with placebo patients, showed a trend in the reduction from baseline at month six in heavy drinking days for the combined trial population of heavy and very heavy drinkers (p="NS)," which was influenced by the high placebo response among very heavy drinkers (avg. 10 drinks per drinking day at baseline), due to both the ad 04 and placebo groups reducing mean heavy drinking days by more than 50%. a similar, non-statistically significant trend was seen in the combined months five and six analysis in the reduction from baseline, which was the pre-specified primary efficacy analysis. iii. at conclusion of the trial, compared with placebo patients, ad 04 patients in the heavy drinking group had an overall significant difference in the severity of their aud diagnosis (p="0.04)" under the diagnostic and statistical manual of mental disorders, fifth edition (dsm-5). for the group of those who no longer meet aud criteria ( less than 2 symptoms), the comparisons were 27.4% vs. 14.9% (i.e., an 84% decrease), of ad04 and placebo patients, respectively. these data underscore the clinical relevance of the findings that heavy drinking aud patients that receive ad 04 appear more likely to recover from the disease by the end of the treatment regimen. iv. based on the levels of alcohol consumption reported in a meta-analysis of 83 prospective studies in primary care screening for those with aud (wood, et. al., lancet 2018), the company estimates that a majority of potential patients for ad 04 would fall under the pre-specified group of heavy drinkers. this finding underscores the potential broad applicability of the results to general practice and that they could be the basis for potential regulatory approvals.

Additionally, and consistent with the Phase IIb trial, AD04 had a safety and tolerability profile that was similar to placebo :Serious Adverse Events (SAEs): i. No SAEs were determined to be related to AD 04 treatment. ii. More SAEs were reported in the placebo group compared with the AD 04 group (7 on placebo vs. 3 on AD 04). iii. There were two cardiac events in placebo group and none in the AD 04 group.

Side effects/Adverse Events (AEs): i. The AE profiles between AD 04 and placebo were similar. ii. AEs reported with a frequency of 5% or more of patients in either group were: headache (11% on placebo, 12% on AD 04), insomnia (3% on placebo, 7% on AD 04), blood magnesium decreased (5% on placebo, 6% on AD 04), and fatigue (3% on placebo, 6% on AD04). All of the above AE’s were reported as mild to moderate. iii. Importantly, in the overall category of cardiac disorders, patients on placebo showed a greater number of adverse events relative to AD 04 (7% on placebo, 4% on AD 04), in addition to greater number of cardiac SAEs in the placebo group as reported above.

Professor Hannu E.R. Alho, Emeritus Professor of Addiction Medicine at the University of Helsinki and Principal Investigator for the ONWARD trial, stated, “These study results may provide hope to millions of people worldwide suffering from AUD, as well to the families of those impacted by this devastating disease. Among heavy drinkers, which make up the majority of my practice, we saw a clear and statistically significant reduction in heavy drinking days for those patients receiving AD 04 versus placebo. These results demonstrate the effectiveness of AD04 for heavy drinker AUD patients.”

Professor. Dr. Bankole Johnson, Chief Medical Officer of Adial, said, “It has been my life mission to develop new therapies that provide patients with a means to either curb the impulse to drink, or abstain from alcohol entirely. AUD accounts for more than 5% of deaths worldwide and is the number one indicator of death for men and women ages 15 to 49, the prime of their lives. The ONWARD study reinforces that AUD is a multi-factorial disease with a diverse set of neurobiological components. The ONWARD data appears to support our earlier findings that AD 04 is a genetically targeted medical treatment addressing the biology of AUD. We believe our finding that AD 04 appears as safe as placebo should increase its acceptability in general practice and eventually lead to widespread adoption of AD 04 for treatment of AUD.”