AD04 for Alcohol Use Disorder: Favorable Feedback From FDA Following End of Phase 2 Meeting

Андрей К/AdobeStock

Adial Pharmaceuticals today announced receipt of the final meeting minutes from its end of phase 2 (EOP2) meeting with the US Food and Drug Administration (FDA) held on July 29, 2025. The minutes provide the FDA's formal input and positive feedback on the AD04 phase 3 adaptive clinical trial design and broader clinical development strategy.¹

The goal of the EOP2 meeting was to align with the FDA on the design of the phase 3 clinical development program for Adial’s lead investigational drug, AD04, a genetically targeted selective serotonin-3 receptor (5-HT3) antagonist and therapeutic agent in development for alcohol use disorder (AUD) in patients who engage in heavy drinking (defined as < 8 drinks/drinking day) and select genotypes.²

"We believe we are at an inflection point in Adial's journey," said Cary Claiborne, president and chief executive officer of Adial. "The successful completion of our end of phase 2 meeting with the FDA has provided critical guidance that strengthens the clinical and statistical framework for our upcoming phase 3 trial of AD04. With regulatory alignment on key protocol elements, including patient population, efficacy endpoints, biomarker stratification, and adaptive enrichment strategies—we are now positioned to advance a streamlined and scientifically rigorous program designed to maximize the probability of success."

The meeting minutes reflect a “constructive dialogue” on AD04. Highlights from the meeting feedback include:

The FDA supported Adial's protocol and proposed adaptive trial design core elements, such as the defined biomarker-positive and biomarker-negative patients, key inclusion criteria targeting moderate to severe AUD, trial duration, primary endpoints, interim analysis sample size, and safety monitoring framework. The FDA also confirmed the proposed primary efficacy endpoints for AD04: 0 heavy drinking days during months 5 and 6 of the efficacy observation period. The FDA was on board with Adial's plan to account for homozygous populations, referencing guidance on developing targeted therapies for low-frequency molecular subsets, with implications for study design and potential labeling of rare subgroups.

The FDA did advise Adial that key secondary endpoints intended for future product labeling should be prespecified in the protocol. The FDA also provided feedback on the planned interim analyses, statistical analysis plan, and data monitoring committee structure.

"This milestone reflects more than regulatory progress—it demonstrates our commitment to precision medicine. By integrating pharmacogenetic insights and validated biomarkers into our development strategy, we are enhancing clinical predictability and setting a new benchmark for targeted therapeutics in neuropsychiatry,” said Claiborne. “This progress, coupled with the recent announcement of our new patent filing for AD04 possibly extending market exclusivity to 2045, frame the AD04 program as an extremely attractive future commercial opportunity with a meaningful patient impact. We remain focused on delivering a transformative solution for patients living with AUD."

Adial is in the process of implementing these FDA recommendations, ensuring readiness to advance toward registrational phase 3 development. The AD04 program is designed for a subset of the population with AUD, patients who are biomarker positive for AG+, identified through Adial's proprietary genetic test. According to research, the AG+ biomarker is present in roughly 14% of the general population.

"As we advance toward phase 3, we believe we are executing from a position of strength across regulatory, clinical, and manufacturing fronts. This milestone is also a catalyst for strategic partnership discussions, which we expect to accelerate with FDA alignment now in place,” concluded Claiborne. “With disciplined execution, we believe AD04 is positioned to become the first genetically targeted therapy for AUD—addressing a large, underserved patient population and unlocking a highly attractive commercial opportunity.”

References

1. Adial Pharmaceuticals provides business update following favorable comments from FDA end-of-phase 2 (EOP2) meeting for AD04. News release. September 16, 2025. Accessed September 16, 2025. https://www.globenewswire.com/news-release/2025/09/16/3150713/26135/en/Adial-Pharmaceuticals-Provides-Business-Update-Following-Favorable-Comments-from-FDA-End-of-Phase-2-EOP2-Meeting-for-AD04.html

2. Kuntz L. End of phase 2 meeting with the FDA: Adial prepares to advance AD04 for alcohol use disorder. Psychiatric Times. August 6, 2025. https://www.psychiatrictimes.com/view/end-of-phase-2-meeting-with-the-fda-adial-prepares-to-advance-ad04-for-alcohol-use-disorder