Date: 2011-06-15
Type of information:
phase: 3
Announcement: results
Company: Lundbeck (Denmark)
Product: nalmefene
Action mechanism: 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.
Disease: alcohol dependence
Therapeutic area: CNS diseases
Country: Europe
Trial details: 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.
Latest
news: Lundbeck has now completed the second 6-months efficacy study in the overall clinical phase III programme with nalmefene. H. Lundbeck has completed 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.
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. 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.
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 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 € 12 million. In total, Biotie is eligible for up to € 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.
