Nalmefene: Changing the treatment of alcohol dependence
About alcohol dependence
Alcohol dependence, otherwise commonly known as alcoholism, is a disease in which the affl icted person continually craves alcohol, is unable to limit his or her drinking, needs to drink greater amounts to get the same effect and has withdrawal symptoms after stopping alcohol use. Alcoholism also has potentially fatal consequences such as liver cirrhosis and cancer1, among others. As a result, this disease is one of the most serious health concerns in the western world, both socially and economically, with estimated associated costs to society of at least EUR 200 billion per annum. 10% of deaths are and 25% of all emergency room admissions in the western world are directly alcohol related. According to the World Health Organization, there are 60 million people in Europe alone who are ‘riskful’ consumers of alcohol, which is categorized as alcohol consumption of 40–60 grams (5–6 standard drinks) by females and 60–100 grams (7–8 standard drinks) by males on a single drinking day. Despite this, alcoholism tends to be severely under-diagnosed with only approximately 13% of alcohol dependants receiving treatment, characterizing it as a large unmet medical need.
Currently, conventional methods of treating alcohol addiction require abstinence from drinking as a starting point – a high hurdle for an alcohol dependence patient. There are only a few pharmaceutical compounds that have received marketing approval to help alcoholics maintain abstinence. All these treatments, including psychosocial counseling measures, cannot prevent a high relapse rate of the patients and permanent cure is thus still the exception rather than the rule.
There are no approved therapies on the market yet to proactively help curb a person’s urge to drink.
Source: 1 National Cancer Institute, Datamonitor (2007), Cognos-Decision Resources (2007)
Nalmefene product profile
Nalmefene is a small molecule, opioid receptor antagonist that inhibits the reward pathway in the brain that reinforces the desire and craving for alcohol and other addictive substances. As a result, nalmefene targets a novel principle in the treatment of alcohol dependence by removing a person’s desire to drink. Nalmefene has been profi led to help patients reduce drinking allowing the patient to take control of his or her addiction, potentially offering patients a realistic and accessible treatment option, and lowering the threshold to enter into treatment. Nalmefene also distinguishes itself by being available as a tablet formulation to be taken on an ‘as needed’ basis, whereas existing pharmaceuticals must be taken continuously over a longer period of time.
Biotie has previously conducted three Phase II studies and two Phase III studies in alcohol dependence. The larger one of the previous Phase III studies, which investigated 400 alcoholic patients in Europe, demonstrated nalmefene's ability to signifi cantly limit both the patient's average alcohol intake and the number of heavy drinking days (intake above fi ve standard drinks of alcohol). Previous trials have also shown nalmefene to be well-tolerated and safe.
Collaboration partner
Biotie and H. Lundeck A/S (Lundbeck) originally entered into a licensing agreement at the end of 2006 for worldwide rights for nalmefene, excluding certain territories which had already been licensed, such as North America, Mexico, UK, Ireland, Turkey, and South-Korea. Since 2008, Lundbeck has acquired the rights to nalmefene from each of the sub-licensees in these territories, including the UK and Ireland license from Britannia Pharmaceuticals (2008), the North-American and Mexican license from Somaxon Pharmaceuticals (2009), and the Turkish license from Eczacıbası Ilac Pazarlama A.S. (2008). Lundbeck now has worldwide rights to nalmefene, excluding South-Korea and as a result, Biotie and Lundbeck have amended their license agreement terms due to the transfer of rights. Under the terms of the amended agreement, Biotie is now eligible for up to EUR 84 million in upfront and milestone payments plus a royalty on potential commercial sales of nalmefene.
Biotie believes Lundbeck is a well-suited commercialisation partner to steer the nalmefene program given the company’s long and deep history in the area of depression and other CNS disorders. Lundbeck was one of the original pioneers to treat clinical depression, recognizing the therapeutic need for patients who had no pharmacological treatment options. Lundbeck plans to build on this expertise to help establish recognition of the medical need and to develop the alcohol dependence market.
Clinical trial status
Lundbeck has three Phase III clinical trials ongoing with nalmefene for the treatment of alcohol dependence with plans to enroll more than 1,800 patients randomized into groups receiving nalmefene or placebo. These studies will support the marketing application for nalmefene to the European Medicines Agency.
Two of the Phase III trials, which are currently enrolling approximately 600 patients each, have effi cacy as primary endpoints. The primary outcome of these studies is a change from baseline in the monthly number of heavy drinking days and in total alcohol consumption over a six month period. We currently expect Lundbeck to report fi rst results from these pivotal trials towards the end of 2010.
The third study, which has enrolled 677 patients is primarily a safety study but effi cacy is also assessed with secondary outcome measures. These include assessment of alcohol consumption and liver enzyme analyses. Biomarkers such as liver enzymes have recently been accepted as secondary endpoints in EMA draft guideline for alcohol dependence studies. Enrollment of patients into this 52-week study was completed in September 2009.
The current patient dossier includes approximately 1,100 patients and will expand to nearly 3,000 patients when the currently ongoing Phase III program is completed.
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Updated March, 2010