ondansetron ultra-low dose (AD04) / Adial - LARVOL DELTA

Adial Pharmaceuticals Receives Positive Response from FDA Meeting Regarding Proposed In Vitro Bridging Strategy for AD04 (GlobeNewswire) - "Adial Pharmaceuticals...announced a positive response from the U.S. Food and Drug Administration (FDA) regarding its proposed in vitro bridging strategy for AD04...The FDA’s feedback follows Adial’s submission on November 19, 2024, in which the Company sought the Agency’s guidance on the alignment of its AD04 formulation strategy and bridging approach. This step is crucial as it ensures compliance with the 505(b)(2) regulatory approval pathway following the completion of the AD04-103 study, a pivotal clinical trial designed to support the drug’s development. The Company also aimed to secure confirmation from the FDA that its proposed data package would meet the necessary bridging requirements and allow for the progression of AD04 into Phase 3 clinical trials....With this regulatory confirmation in place, Adial is proceeding with the manufacturing of clinical supply materials in preparation for its upcoming Phase 3 clinical program in 2025."

FDA event • New P3 trial • Addiction (Opioid and Alcohol) • CNS Disorders

Adial Pharmaceuticals Granted New U.S. Patent Expanding Coverage of its Genetic-Based Approach to Treating and Diagnosing Alcohol Use Disorder and Other Drug Dependencies (GlobeNewswire) - "Adial Pharmaceuticals, Inc...today announced patent number 12,226,401 was issued on February 18, 2025 by the United States Patent and Trademark Office (USPTO) expanding coverage of Adial’s genetic-based approach to treating and diagnosing alcohol use disorder and other drug dependencies. The new patent covers claims that focus on a method for identifying genetic markers in patients with alcohol or opioid-related disorders. With the identification of specific genotypes, including the AC genotype of rs17614942 in the HTR3B gene and the AG genotype of rs1150226 in the HTR3A gene, providers will be able to provide tailored treatment plans using AD04, the Company’s investigational new drug product."

Patent • Addiction (Opioid and Alcohol) • CNS Disorders

Adial Pharmaceuticals Awarded New U.S. Patent Covering Genotype-Specific Treatment of Opioid-Related Disorders (GlobeNewswire) - "Adial Pharmaceuticals, Inc...today announced patent number 12,221,654 was issued on February 11, 2025, by the United States Patent and Trademark Office. This patent expands the covered methods of identifying patients with specific genetic markers linked to substance use disorders and treating them with AD04, the Company’s investigational new drug product. The treatment approach involves detecting the TT genotype of rs1042173 in the serotonin transporter gene (SLC6A4) and administering AD04. These treatment methods are tailored for individuals suffering from disorders such as opioid dependence, opioid abuse, alcohol dependence, and other related conditions."

Patent • Addiction (Opioid and Alcohol) • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "Based on these preclinical results we conclude that AD04 administration induces microglia to phagocytose brain debris, such as apoptotic neurons, synapses and degraded myelin in the aged brain, and in the AD brain also Abeta, extracellular tau tangles and oxidized lipids. By changing the microglial phenotype, AD04, indirectly reduces the neuroinflammation induced by Abeta, tau and neuronal debris, leading to an anti-inflammatory milieu in the brain which protects and rescues the hippocampus from neurodegeneration."

IO biomarker • Journal • Allergy • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Metabolic Disorders

AD04 Global HIV migration (AIDS 2024) - "Our stories set the stage for a set of keynote speakers who highlighted the political, policy and programmatic challenges that continue to face people living with HIV if they wish to migrate or simply travel to other countries.The hugely influential Global Database on HIV-specific Travel and Residence Restrictions (hivtravel.org) will soon have a new look and home with the HIV Justice Network. Your stories will help shape this revamp.Now is the chance for you to share your story.The booth is hosted by the HIV Justice Network, Queensland Positive People, National Association of People Living with HIV Australia and Global Database on HIV-specific Travel and Residence Restrictions."

Clinical • Human Immunodeficiency Virus • Infectious Disease

AD04 – modifying Alzheimer’s Disease by modulation of neuroinflammation (AAIC 2024) - "Based on these preclinical results we conclude that AD04 administration induces microglia to phagocytose brain debris, such as apoptotic neurons, synapses and degraded myelin in the aged brain, and in the AD brain also Abeta, extracellular tau tangles and oxidized lipids. By changing the microglial phenotype, AD04, indirectly reduces the neuroinflammation induced by Abeta, tau and neuronal debris, leading to an anti-inflammatory milieu in the brain which protects and rescues the hippocampus from neurodegeneration."

IO biomarker • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Metabolic Disorders

Low-dose ondansetron: A candidate prospective precision medicine to treat alcohol use disorder endophenotypes. (PubMed, Eur J Intern Med) - "In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure."

Clinical • Journal • Addiction (Opioid and Alcohol)

"Time Saved" Calculations to Improve Decision-Making in Progressive Disease Studies. (PubMed, J Prev Alzheimers Dis) - "The relevance of 11 months saved is more universally understood than a mean difference of 3.8 points in the composite outcome. These results suggest that a combination of a composite approach and a time savings interpretation offers a powerful approach for detecting and interpreting disease modifying effects."

Clinical • Journal • P2 data • Alzheimer's Disease • CNS Disorders

Safety and compliance of long-term low-dose ondansetron in alcohol use disorder treatment. (PubMed, Eur J Intern Med) - "Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD."

Compliance • Journal • Addiction (Opioid and Alcohol) • Hepatology • Liver Failure

DESIGN OF A RANDOMIZED PHASE 2B, PLACEBO-CONTROLLED TRIAL ASSESSING SAFETY AND EFFICACY OF AD04 IN EARLY ALZHEIMER'S DISEASE ("ADVANCE") (ADPD 2024) - "The ADVANCE RCT is evaluating a novel immune-stimulating intervention for patients with early AD, based on evidence from AFF006 (phase 2). The study has a high estimated probability of success."

Clinical • P2b data • Alzheimer's Disease • CNS Disorders

Time saved in disease progression for treatments in AD (including 3 monoclonal antibodies and 2 other promising treatments) (AAIC 2023) - " Results for five studies of interest (three monoclonal antibodies and two other treatments) Aducanumab, Donanemab, Lecanemab, AD04, and Souvenaid show time savings range from 2 months per year to 7 months per year. Measuring time savings in a degenerative disease reflects the true goal of disease modifying treatments which is to slow down a progressive disease which will result in slowing of progression on all aspects or symptoms of disease. Progressive diseases would cease to be diseases at all if there was no progression of symptoms. Focusing on the clinical meaningfulness of each separate point on each outcome distracts us from this overall goal."

Alzheimer's Disease • CNS Disorders

Targeting USP7 in Colorectal Cancer (EACR 2023) - "We also investigate how AD04 impacts response to the backbone of standard-of-care 5-Fluorouracil (5FU) treatment and how this is affected by interactions within the tumour microenvironment. Moreover, co-cultures with activated T-cells further enhanced the effects of AD04/5FU in both 2D and 3D co-cultures. Although this immune cell-mediated enhancement was a caspase-dependent process, indicative of apoptosis, no enhanced expression of pro-apoptotic p53-target genes such as PUMA was observed in the co-treatment group compared to 5FU alone.ConclusionAltogether, these results reveal a novel synergism between USP7 inhibition and 5FU that is independent of p53 in vitro."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CDKN1A • CTNNB1 • UHRF1 • USP7

"$ADIL $ADILW Adial Pharmaceuticals Engages The Keswick Group to Advance Partnering Activities for the Clinical Development of AD04 for Alcohol Use Disorder https://t.co/n7WPtsad2r" (@stock_titan)

Clinical • Addiction (Opioid and Alcohol)

Adial Pharmaceuticals Confirms Scheduling of Meetings with FDA and European Regulatory Agencies to Advance Clinical Development of AD04 for Alcohol Use Disorder (GlobeNewswire) - "Adial Pharmaceuticals...announced that it has secured meetings with regulatory authorities in the U.S. and Europe to discuss and develop plans for the clinical advancement of AD04 for alcohol use disorder toward potential approvals. In the United States, Adial has secured a Type C meeting with the Food and Drug Administration (FDA) in the second quarter of this year. This meeting will allow Adial and the FDA to discuss the clinical development program for AD04 in the U.S. and the most appropriate path toward possible approval. In Europe, Adial has meetings scheduled or planned with five national regulatory authorities in France, Sweden, Finland, the United Kingdom and Germany. Adial intends to seek from the agencies a clear understanding and direction toward the most expeditious path to approval."

European regulatory • FDA event • Addiction (Opioid and Alcohol) • CNS Disorders

AD04 respiratory infectiology (CPLF 2023) - No abstract available

ONWARD: Study to Evaluate AD04 in Adults With Alcohol Use Disorder (AUD) and Selected Serotonin Transporter Polymorphisms (clinicaltrials.gov) - P3 | N=302 | Completed | Sponsor: Adial Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Addiction (Opioid and Alcohol) • SLC6A4

ONWARD: Study to Evaluate AD04 in Adults With Alcohol Use Disorder (AUD) and Selected Serotonin Transporter Polymorphisms (clinicaltrials.gov) - P3; N=302; Active, not recruiting; Sponsor: Adial Pharmaceuticals; Recruiting ➔ Active, not recruiting; Trial completion date: Sep 2021 ➔ Feb 2022; Trial primary completion date: Jul 2021 ➔ Jan 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

"$ADIL $ADILW Adial Pharmaceuticals Awarded U.S. and International Patents for the Treatment Of Alcohol and Opioid Use Disorders Using AD04 https://t.co/UkE8E8PAgY #patent" (@stock_titan)

Addiction (Opioid and Alcohol) • Substance Abuse

The Phase 3 ONWARD Trial Meets its Screening Target and Nears Enrollment Completion (GlobeNewswire) - P3, N=290; ONWARD (NCT04101227); Sponsor: Adial Pharmaceuticals; "Adial Pharmaceuticals, Inc...today announced that the Company has made significant progress on its pivotal ONWARD Phase 3 clinical trial having met 100% of its patient screening target and having achieved 90% of its patient enrollment target. The ONWARD trial is evaluating AD04 as a therapeutic agent for the treatment of Alcohol Use Disorder (AUD) in persons with certain target genotypes related to the serotonin transporter and receptor genes...While the trial is still blinded so it is not known which patients are taking AD04 or placebo, the vast majority of adverse events reported across all study subjects are mild in intensity."

P3 data • Trial status • Addiction (Opioid and Alcohol) • CNS Disorders

"$ADIL $ADILW Adial to File Fast Track Application for AD04 with the FDA https://t.co/DqwYvuUnFv" (@stock_titan)

A randomized, double-blind, placebo-controlled proof-of-concept study of ondansetron for bipolar and related disorders and alcohol use disorder. (PubMed, Eur Neuropsychopharmacol) - "However, the findings suggest that ondansetron may be associated with reduction in depressive symptom severity in persons with bipolar illnesses and alcohol use disorder. A larger trial is needed to examine the effects of ondansetron on bipolar depression."

Clinical • Journal • Addiction (Opioid and Alcohol) • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

"$ADIL $ADILW Adial Pharmaceuticals Announces FDA Reactivation of its Investigational New Drug Application for AD04 in Alcohol Use Disorder https://t.co/7JudIo5YTi" (@stock_titan)

IND • Addiction (Opioid and Alcohol)

Selecting an appropriate alcohol pharmacotherapy: review of recent findings. (PubMed, Curr Opin Psychiatry) - "Three new published RCTs focus on baclofen and naltrexone. These results are consistent with old findings demonstrating that naltrexone reduces heavy drinking. Several RCT on baclofen do not support the use of baclofen for treatment of AUD. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence."

Journal • Addiction (Opioid and Alcohol) • Nicotine Addiction

Pharmacogenetic Study of Ondansetron in Alcohol Use Disorder (clinicaltrials.gov) - P2; N=293; Completed; Sponsor: University of Maryland, Baltimore; Recruiting ➔ Completed; Trial completion date: Dec 2021 ➔ Mar 2020; Trial primary completion date: Dec 2020 ➔ Mar 2020

Biomarker • Clinical • Trial completion • Trial completion date • Trial primary completion date

Ondansetron for Bipolar Disorder and Alcohol Use Disorders (clinicaltrials.gov) - P4; N=70; Recruiting; Sponsor: University of Texas Southwestern Medical Center; Trial primary completion date: Jan 2017 ➔ Feb 2018

Trial primary completion date • Biosimilar • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders