Euthymics is developing products for central nervous system disorders of significant unmet medical need – including alcohol use disorder and smoking cessation – under a collaboration with the government. AUD is a serious disorder with 2.5 million individuals (75,000 Americans) dying each year from alcohol-related events. Smoking cessation: About half of the nearly 60 million smokers attempt to quit each year. The CDC estimates that smoking-related illnesses cost nearly $170 billion each year. Learn more about addiction >
Several phase 2 randomized clinical trial of amitifadine (ATN) for AUD are currently being planned at five National Institute on Alcohol Abuse and Alcoholism (NIAAA) Centers of Excellence. Our trial will focus on heavier use AUD.
Several trials are planned evaluating ATN to aid smoking cessation. These trials would be in collaboration with the National Institute on Drug Abuse (NIDA).
AN EFFECTIVE TREATMENT FOR ALCOHOL USE DISORDER (AUD) must address repeated alcohol use that typically includes a strong desire to take alcohol, difficulties in controlling its use, persisting in its use despite harmful consequences.
FOR SMOKING CESSATION nicotine specifically increases levels of dopamine in the reward circuits. However, an effective treatment must also address associated withdrawal symptoms including irritability, craving, depression, anxiety, cognitive and attention deficits, sleep disturbances, and increased appetite.
Because addiction is a chronic condition, there is no one-time cure. Therefore, medications must be tolerable, preferably oral, and taken long-term.
Previous clinical trials (for depression) demonstrated amitifadine overall was well tolerated and results indicate no dose limiting adverse effects found in doses used in the studies.
Amitifadine (ATN, formerly EB-1010) is a triple reuptake inhibitor with the greatest potency towards serotonin reuptake (5-HT), half as much towards norepinephrine reuptake (NE) and one eighth towards dopamine reuptake (DA).
“Addiction is a chronically relapsing disorder characterized by a compulsion to seek and take a drug, loss of control in limiting intake and emergence of a negative emotional state (for example, dysphoria, anxiety and irritability) when access to the drug is prevented.” Development of Pharmacotherapies for Drug Addiction: a Rosetta Stone Approach, George F. Koob, June 2009
AMITIFADINE IN ALCOHOL USE DISORDER
- Impulsivity is involved in addictive behaviors including alcoholism (Mitchell et al., 2007)
- Compounds that modulate NOREPINEPHRINE transporters may decrease impulsivity
- This and preclinical findings in models of addiction suggest amitifadine would reduce impulsivity in addiction including AUD which could manifest itself in less impulsive drinking
- Chronic alcoholics have a greater than 90% lifetime diagnosis of psychiatric disorders including depression and anxiety
- SEROTONIN function is reduced in alcoholics and serotonin neurotransmission would be improved by amitifadine
Alcohol Use Disorder (AUD) is a new DSM-V diagnosis and combines alcohol abuse and alcohol dependence. AUD is highly prevalent with a US prevalence of 8.5% translating to approximately 16 million adults in the US
Regulatory views on developing treatments have progressed
Existing medications have focused on abstinence and have low efficacy with poor adherence
Recognizing that achieving and then maintaining abstinence in an addictive disorder is challenging, the FDA recently moved from using total abstinence as the primary end-point for pivotal phase 3 trials to using the percent of subjects with no heavy drinking days. The EMA has taken a similar position.
In preclinical studies, ATN shows a dose-related reduction in alcohol intake.
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is the Federal agency responsible for US government research efforts on alcohol use and abuse. The NIAAA conducted a comprehensive preclinical research program on amitifadine and found it has beneficial potential in AUD
AMITIFADINE IN NICOTINE ADDICTION/SMOKING CESSATION
ATN shows similar potential to help people quit smoking tobacco with efficacy at the same dosing anticipated for alcohol use disorder
Large market potential: According to NIDA 35 million people each year express the desire to quit smoking cigarettes. More than 85% of those who try to quit smoking on their own relapse shortly after quitting. 2015 US sales of Chantix are on track to exceed $500M.