Lundbeck has now completed the second 6-months efficacy study in the overall clinical phase III programme with nalmefene
Nalmefene has a significant potential for helping individuals with alcohol dependence in reducing their alcohol consumption and allowing individuals to be in control of their alcohol intake
The reduction in heavy drinking days and total alcohol consumption was seen within the first month of treatment in all three studies and was maintained throughout the 12-month safety study
Nalmefene was safe and well tolerated
Nalmefene is the first medicine aimed at regulatory approval in Europe for the reduction of alcohol consumption in patients with alcohol dependence consequently reducing the risk of alcohol related harm
Submission of an MAA for nalmefene in Europe is expected by the end of 2011
H. Lundbeck A/S (Lundbeck) today announced the completion of the final study (ESENSE2) in the phase III clinical programme for nalmefene in patients with alcohol dependence. In this multi-center, double-blind, placebo-controlled study, 718 individuals were randomized to receive oral administration of 20 mg of nalmefene or placebo on an as-needed basis for a total of 28 weeks of treatment.
"We are pleased that we now have reached a stage with nalmefene where we can plan the regulatory process with an expected submission of the MAA towards the end of the year" says Executive Vice President Anders Gersel Pedersen, Head of Drug Development at Lundbeck, and continues: "Across the clinical phase III programme consistency and robustness were observed and the studies support the overall positive clinical profile of nalmefene".
During the clinical programme a wide range of primary and secondary endpoints were assessed, including number of heavy drinking days per month (HDD), total alcohol consumption in grams per day (TAC), proportion of responders based on drinking measures, alcohol dependence symptoms and clinical status, liver function and other laboratory tests, pharmaco-economic outcomes and treatment discontinuation effects. All assessments were consistently in favour of nalmefene compared to placebo, though some were not statistically significant at every single time point. It was consistently observed that the medical intervention with nalmefene had a strong effect that was seen within the first month and led to a reduction in alcohol consumption of over 50% and was maintained throughout the study periods.
The three studies in the overall phase III clinical programme were conducted in Europe and enrolled about 2,000 individuals with alcohol dependence. A medical compliance encouragement programme was included in all treatment arms in the studies. No abstinence treatment goals were imposed. The data from ESENSE2 is consistent with the profile seen in previous clinical studies of nalmefene. In all three clinical studies the overall safety profile of nalmefene was consistent with observations and data provided in previous studies making a total clinical database of more than 3,000 individuals. The most frequent adverse events included dizziness, insomnia and nausea and were mild and transient upon stopping treatment.
Heavy drinking level is defined as five or more drinks per day for men and four or more drinks per day for women. Individuals on 20 mg nalmefene had after 6 months of treatment a decrease of heavy drinking days by more than 50%. Furthermore, data from the 12 month safety study (SENSE) confirmed that this effect is maintained and even improved after 1 year of treatment; leading to more than 60% overall reduction in total alcohol consumption. Approximately 2/3 of the individuals in the studies have not been treated for alcohol dependence before, indicating that reduction of alcohol intake is an attractive alternative treatment objective compared to current treatments which all require abstinence.
Lundbeck plans to submit a European Marketing Authorization Application (MAA) for nalmefene as a treatment for alcohol dependence towards the end of 2011. The presentation of the efficacy and safety data at scientific meetings and conferences is planned during the next 12 months.
Nalmefene builds on a novel principle of treating alcohol dependence. Unlike existing therapies, the treatment with nalmefene can be used on an as-needed basis allowing individuals to be in control of their treatment and limit the intake of alcohol rather than requiring full abstinence. Reduction of alcohol consumption to less harmful levels is supported by specialists as a valuable treatment option to keep the individuals in treatment and to increase the willingness among patients to initiate treatment. In addition, nalmefene distinguishes itself by being available as a tablet formulation to be taken only according to need, whereas existing pharmaco-therapies must be taken continuously over a longer period of time and with the aim of maintaining abstinence.
About the clinical phase III programme
Based on the results of earlier trials, Lundbeck initiated three phase III clinical studies in Europe in 2008 enrolling a total of approximately 2,000 individuals randomised into two groups receiving nalmefene (20 mg as needed, orally) and placebo in addition to a brief medical compliance encouragement programme. Two of the three trials (ESENSE1 and ESENSE2), in which individuals were treated over a period of six months, primarily aimed to demonstrate the efficacy of nalmefene, whilst the primary objective of the third study (SENSE), in which individuals were treated for 12 months, was to confirm the safety and tolerability of the compound.
Nalmefene is a selective opioid receptor ligand with antagonist activity at mu and delta opioid receptors and partial agonistic activity at the kappa opioid receptor. This pharmacological profile helps to control and reduce alcohol intake.
Nalmefene was originally developed by Key Pharmaceuticals and IVAX/Baker Norton in the 1980s and 1990s. Biotie Therapies Corp. (Biotie) in Finland obtained the rights to the compound in 1998 and started clinical development within alcohol disorders in 1999. In 2006, Lundbeck licensed the rights to nalmefene from Biotie. Under the terms of the agreement, Biotie received an execution fee of EUR 12 million. In total, Biotie is eligible for up to EUR 84 million in upfront and milestone payments plus royalty on sales. Lundbeck will be responsible for manufacturing and registration of the product.
Lundbeck holds the global rights to the compound.
About alcohol dependence
Alcohol dependence is a disorder of the central nervous system with a chronic, relapsing, and often progressive course. Alcohol affects chemical pathways in the brain, and long-term exposure increases the rewarding effects of alcohol and reduces the control over consumption in vulnerable people. Research suggests that genetic and environmental factors contribute about equally to the risk of developing alcohol dependence.
Alcohol is toxic to most organs, and its use is linked to several diseases including cancer and cardiovascular diseases. Alcohol is a significant threat to public health, social welfare and economic development. It is estimated that in any given year, 5.0% of adult men and 1.4% of adult women in the EU will suffer from alcohol dependence, with large differences across nations.
The content of this release will have no influence on the Lundbeck Group's financial guidance for 2011 which was provided on 24 February 2011 in connection with the release of the financial results for 2010.