acamprosate/baclofen (PXT-864) / Pharnext - LARVOL DELTA

Low dose baclofen and standard dose acamprosate had comparable changes in brain glutamate, brain Gamma amino butyric acid (GABA) and craving among patients with alcohol dependence syndrome: A 1H-MRS based open label randomized study. (PubMed, Ind Psychiatry J) - "Our study has shown comparable changes in Glutamate and GABA during the early post-detoxification period both for baclofen and acamprosate. Effects of baclofen and acamprosate might correlate differently with the clinical profile of alcohol dependence syndrome which would help in choosing a particular anticraving medication."

Journal • Addiction (Opioid and Alcohol)

HEPATOLOGY AND NON-HEPATOLOGY PRESCRIPTION OF MEDICATION-ASSISTED TREATMENT FOR ALCOHOL USE DISORDER IN ALCOHOL-ASSOCIATED LIVER DISEASE YIELD SIMILAR OUTCOMES (DDW 2025) - " We performed a retrospective chart review of individuals diagnosed with ALD and AUD by ICD10 codes who were prescribed MAT (naltrexone, acamprosate, baclofen or gabapentin) from 2022-2024 at a tertiary care, liver transplant center. Outcomes after MAT therapy are not significantly different regardless of the specialty of the prescribing team. Our results support a more active role for GI/hepatology in MAT prescription in those with ALD and AUD."

Addiction (Opioid and Alcohol) • Hepatology

Introduction: Approved treatments for alcohol use disorder by regulatory agencies. (PubMed, Int Rev Neurobiol) - "Currently, only a few medications, such as disulfiram, naltrexone, nalmefene, and acamprosate, are approved to treat AUD. Moreover, genetic factors and comorbid conditions can significantly influence both the development of AUD and the efficacy of its treatment. This chapter explores the genetic underpinnings of AUD and reviews the main pharmacological treatments available for managing this disorder."

Journal • Review • Addiction (Opioid and Alcohol)

ALCOHOL INTERVENTION AFTER ACUTE VARICEAL BLEEDING: REDUCES ALCOHOL CONSUMPTION, BUT REMAINS UNDERUTILIZED IN REAL-WORLD SETTING (AASLD 2024) - "Alcohol intervention is defined as either the use of pharmacological treatment (Naltrexone, acamprosate, baclofen and gabapentin), or referral to psychologists or addiction service. Alcohol intervention was associated with a reduction in alcohol use among ALD cirrhosis patients in the real-world setting. Given the potential of patients with decompensated ALD cirrhosis to recompensate after alcohol abstinence, our findings highlight the gap in improving the uptake of AUD intervention in this cohort."

Clinical • Real-world • Real-world evidence • Addiction (Opioid and Alcohol) • CNS Disorders • Fibrosis • Hepatology • Immunology • Psychiatry

Alcohol, tobacco, and cannabis use in patients with borderline personality disorders admitted in an emergency department (ECNP 2024) - "Only two patients received pharmacological treatments for alcohol cessation, namely acamprosate and baclofen... The rates of patients admitted for suicidal behaviors or benzodiazepine intoxication, and the rates of alcohol daily use were higher in the group of patients with borderline personality disorders than in the group of controls. Tobacco and cannabis daily use were frequent in patients with borderline personality disorders admitted in an emergency department, but not significantly compared to the group of controls. In contrast, the rate of patients receiving treatments for alcohol or nicotine use disorders were very low."

Clinical • Addiction (Opioid and Alcohol) • Borderline Personality Disorder • CNS Disorders • Depression • Mood Disorders • Nicotine Addiction • Personality Disorder • Psychiatry • Tobacco Cessation

Achieving abstinence: Prescribing AUD medications in ARLD (AGW-GESA 2024) - "Each patient was prescribed either acamprosate, baclofen, gabapentin or naltrexone. Patients receiving AUD medication mostly reduce their alcohol consumption with a fifth of patients achieving abstinence. Whilst some patients ceased medications within the follow-up period, there was still an overall reduction in alcohol consumption within the group. Given this positive initial response to medication, addressing compliance and tolerability in the clinical setting is paramount to achieving success with these medications."

Addiction (Opioid and Alcohol) • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

UTILIZING A NOVEL TELEHEALTH PLATFORM TO CHARACTERIZE AND DETERMINE OUTCOMES FOR POST-WEIGHT LOSS SURGERY PATIENTS WITH ALCOHOL USE DISORDER (DDW 2024) - "MAT included naltrexone gabapentin topiramate baclofen or acamprosate alone or in combination. Behavioral and pharmacologic interventions tailored for this susceptible demographic yielded reductions in heavy drinking days and WHO risk levels while exhibiting no statistically significant disparities when compared to the non-WLS population. This underscores the importance of involving post-WLS patients in AUD care to mitigate the risk of liver disease in this high-risk group."

Bariatric surgery • Clinical • Surgery • Addiction (Opioid and Alcohol) • Genetic Disorders • Hepatology • Obesity

Role of Acamprosate and Baclofen as Anti-craving Agents in Alcohol Use Disorder: A 12-Week Prospective Study. (PubMed, Cureus) - "For other variables being considered in the study, namely, days to first alcohol consumption, days to relapse to previous drinking pattern, number of patients who dropped from the study versus those who completed the study, and those who were abstinent versus those who relapsed, no statistically significant difference was noted. Conclusion Acamprosate-treated patients had significantly lesser cravings for alcohol and consumed a lesser number of drinks on one occasion compared to baclofen-treated patients in this 12-week study."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

A systematic review of interventions for alcohol use disorder in patients with cirrhosis or alcohol-related hepatitis (EASL-ILC 2023) - "Other interventions were pharmacological (baclofen, acamprosate, naltrexone, faecal transplant), psychological (motivational therapy, educational sessions) and attendance at specialist clinics. Interventions for alcohol use disorder can be effective in improving clinical outcomes of patients with cirrhosis and alcohol related hepatitis. The evidence base is dominated by large database derived cohorts and the interventions are not well defined, indicating the need for further research in this area. Figure: RCTs in the review Reference Country Age (Mean or Median) Male s n Intervention Outcomes Follow up Sussman 2005 USA 44 75% 2 5 Educational sessions Alcohol only 3 months Addolorato 2007 Italy 56 64% 8 4 Baclofen Alcohol only 90 days Bajaj 2021 USA 65 100 % 2 0 Faecal Transplant Alcohol and Liver Disease 6 months DeMartini 2018 USA 50.8 73% 1 5 Text message- based alcohol intervention Alcohol only 8 weeks Proeschold-Bell 2020 USA 54.9 71.3 % 5 8 Alcohol Treatment..."

Clinical • Review • Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Transplantation

Pharmacological Inventions for Alzheimer Treatment in the United States of America: A Revision Patent from 2010 - 2020. (PubMed, J Prev Alzheimers Dis) - "The molecules Elenbecestat and LY3202626 decreased the burden of Aβ plaques without significant cognitive improvement, Donanemab is in Phase 3 clinical trial, and the FDA has designated it Breakthrough Therapy. CPC-201 and PXT864 demonstrated, in Phase 2, good tolerability and improvement of AD symptoms...The most advanced treatments in their research are those focused on treating Aβ accumulation. More studies are needed to prove the efficacy of the patented molecules."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Immunology • Inflammation

Baclofen for alcohol use disorder. (PubMed, Cochrane Database Syst Rev) - "Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason or due to adverse events. It probably does not reduce number of heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in maintaining abstinence. The results of comparisons of baclofen with acamprosate and naltrexone were mainly based on only one study."

Journal • Review • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Depression • Fatigue • Mental Retardation • Mood Disorders • Psychiatry • Xerostomia

The use of pharmacotherapy in the treatment of alcohol use disorder (EASL-ILC 2022) - "This survey collected demographic information and assessed prescribing habits towards medications which have been approved to treat AUD (Naltrexone, Disulfiram, Baclofen, Librium, Nalmefene and Acamprosate)...Librium was commonly used by 88% (n = 53), while <10% regularly prescribed Naltrexone, Baclofen, or Acamprosate... Despite the burden of alcohol on our acute hospitals, there is a clear and significant lack of support for alcohol related conditions. Emanating from this is the underutilisation of pharmacotherapy as a treatment for AUD, despite its evidence base. This survey highlights an urgent need to develop alcohol support services, in conjunction with physician education about the role of pharmacotherapy in treating AUD."

Addiction (Opioid and Alcohol) • Gastroenterology • Hepatology

Acamprosate may be safer than baclofen for the treatment of alcohol use disorder in patients with cirrhosis: a first description of use in real-world clinical practice. (PubMed, Eur J Gastroenterol Hepatol) - "In patients with cirrhosis, acamprosate was associated with fewer unplanned admissions than baclofen, hence may be safer despite historical concerns."

Journal • Real-world evidence • Addiction (Opioid and Alcohol) • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

[VIRTUAL] Acamprosate for the treatment of alcohol use disorder may be safer than baclofen in patients with cirrhosis (EASL-ILC 2021) - "We performed an audit to compare the safety of acamprosate to baclofen. We describe, for the first time, acamprosate use in cirrhotic patients in clinical practice. Acamprosate may be safer than baclofen, although prospective confirmation is required."

Clinical • Addiction (Opioid and Alcohol) • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis • Liver Failure

A comparative study on the safety and efficacy of naltrexone versus baclofen versus acamprosate in the management of alcohol dependence. (PubMed, Indian J Psychiatry) - "The efficacy of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence has been successfully established over the past several years...Naltrexone group reported the least number of relapses but maximum number of side effects. Acamprosate group had the maximum dropout rate."

Clinical • Journal • Addiction (Opioid and Alcohol)

Combination of acamprosate and baclofen (PXT864) as a potential new therapy for amyotrophic lateral sclerosis. (PubMed, J Neurosci Res) - "The only approved treatments are riluzole and edaravone, but their efficacy is modest and short-lasting, highlighting the need for innovative therapies. The anti-TDP-43 aggregation effect was also confirmed in a cell line expressing TDP-43 fused to GFP. These results demonstrate the value of PXT864 as a promising therapeutic strategy for the treatment of ALS."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • Movement Disorders • Parkinson's Disease

Pharnext to present latest scientific data on its two lead assets at several international scientific conferences (Businesswire) - “Drug candidate PXT864, in clinical development for the treatment of Alzheimer’s disease, will be highlighted in two posters and three oral presentations….Pharnext will…discuss the Company’s Phase 2 trial of PXT864 for the treatment of Alzheimer’s disease.”

Pipeline update • Alzheimer's Disease • CNS Disorders

Pharnext's pleodrug PXT-864 demonstrates positive effects in Parkinson's disease preclinical data published in Nature's Scientific Reports (PRNewswire) - "Pharnext SAS today announced the publication of positive preclinical results in Nature'sScientific Reports for its pleodrug PXT-864 in Parkinson's disease. PXT-864 may represent an efficient and valuable strategy to slow or stop the progression of Parkinson's disease. In addition, PXT-864 could also improve symptoms of patients without inconvenience related to L-Dopa treatment. "The data presented provide compelling evidence of PXT-864's potential in the treatment of Parkinson's disease....I look forward to the clinical development of PXT-864 to see if these effects can be translated to patients with Parkinson's disease."

Preclinical • Parkinson's Disease

Pharnext : To present new PXT864 synergy data at AD/PDTM 2017, the 13th International Conference on Alzheimer‘s and Parkinson‘s Diseases and Related Neurological Disorders (Valliant News) - "Pharnext...today announced that positive preclinical data for its PLEODRUG™ PXT864, in development for Alzheimer’s disease (AD), will be presented at the AD/PDTM 2017 congress on March 29 – April 2 in Vienna, Austria."

Preclinical

A Potential TRI-Therapy for Alzheimer’S Disease (AAIC 2019) - "In this study, we investigated whether PXT864 could i) protect cognitive functions by synergizing with sub-therapeutic doses of donepezil (DNPz) to limit the occurrence of adverse events, or ii) rescue the efficacy of DNPz that is lost over time under therapeutic doses. These data highlight the importance of combinational strategies and suggest that PXT864 could be used either as a first line treatment or a second line treatment with a safe sub-therapeutic or even a full therapeutic dose of DNPz in Alzheimer’s patients."

"Good evening @pfizer, what do you think of the pxt864 @pharnext, in addition to a take aricept please?" (@smartiiiie)

A POTENTIAL TRI-THERAPY FOR ALZHEIMER’S DISEASE (ADPD 2019) - "In this study, we investigated whether PXT864 could i) protect cognitive functions by synergizing with sub-therapeutic doses of donepezil (DNPz) to limit the occurrence of adverse events, or ii) rescue the efficacy of DNPz that is lost over time under therapeutic doses. Interestingly, adding PXT864 at that stage fully restored lost cognition in these animals that became all irresponsive to DNPz. These data highlight the importance of combinational strategies and suggest that PXT864 could be used either as a first line treatment or a second line treatment with a safe sub-therapeutic or even a full therapeutic dose of DNPz in Alzheimer’s patients."

A COMBINATION OF ACAMPROSATE AND BACLOFEN (PXT864) AS A POTENTIAL NEW THERAPY FOR AMYOTROPHIC LATERAL SCLEROSIS (ADPD 2019) - "Importantly, PXT864 added to riluzole significantly improved such protection against glutamate-induced damages. These results demonstrate the potential value of PXT864 as a promising therapeutic strategy for the treatment of ALS."