Lundbeck is pleased to announce the launch of Selincro (nalmefene), the first medicine approved for the reduction of alcohol consumption in alcohol-dependent patients with a high drinking risk level.1
The endogenous opioids play a key role in the rewarding (addictive) properties of ethanol by activation of the mesolimbic dopamine system. Nalmefene is an opioid system modulator with antagonist activity at the µ and d receptors and partial agonist activity at the k receptor.
The approval follows the results of a post hoc analysis of two randomised controlled 6-month studies (ESENSE 1 and ESENSE 2) designed to evaluate the efficacy and safety of as-needed nalmefene in reducing alcohol consumption in alcohol-dependent patients with a high drinking risk level.
Rationale
ESENSE 1 and ESENSE 2 have shown that nalmefene as-needed reduces the total amount of alcohol consumption and number of heavy drinking days in patients with alcohol dependence. However, in both studies a significant proportion of patients (18%, and 33%, respectively) considerably reduced their alcohol consumption in the first two weeks between the initial visit (screening) and randomisation. At randomisation, these patients consumed such a small amount of alcohol that there was little room for further improvement (floor effect), resulting in a substantial underestimation of the treatment effect.
This population of patients may represent excessive drinkers who after making the decision to seek help can reduce their drinking with minimal intervention. Taking this phenomenon into account, a post hoc analysis was designed which included the subgroup of patients who continued their high level of alcohol consumption after initial assessment until the start of treatment, as these were expected to derive the highest clinical benefit from nalmefene.
Study design
The post hoc analysis included a pooled population of 667 patients (from ESENSE 1 and ESENSE 2) who did not reduce their alcohol consumption after an initial assessment, i.e. with at least a high drinking risk level (men: >60g/day; women: >40g/day) at both screening and randomisation. Nalmefene 18mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Data on clinical improvement, liver function and safety were also collected throughout the study.
Daily alcohol consumption reduced from more than 100g/day to 40g/day with Selincro*
Nalmefene as-needed was found to be superior to control in reducing daily alcohol consumption. Mean baseline values were approximately 100g/day for alcohol consumption in ESENSE 1 and 110g/day in ESENSE 2. For the pooled target population (Figure A), the estimated mean reduction from baseline in total alcohol consumption at Month 6 was -51.4g/day for the control group and -65.7 g/day for the nalmefene group, corresponding to a treatment effect of -14.3 g/day (p < 0.0001) in favour of nalmefene.
Number of heavy drinking days reduced from 23 days to 10 days per month with Selincro
Benefits similar to those obtained for total alcohol consumption were observed for the number of heavy drinking days. At baseline, the mean number of heavy drinking days was approximately 23 days/month in ESENSE 1, and 22 days/month in ESENSE 2. For the pooled target population (Figure B), the estimated mean reduction in heavy drinking days at Month 6 was -9.4 days/month for the control group and -12.6 days/month for the nalmefene group, corresponding to a treatment effect of -3.2 heavy drinking days/month (p < 0.0001) in favour of nalmefene.
For both co-primary outcomes, the magnitude of the treatment effect was greater in the target population of high risk drinkers than in the total treatment population (in both trials separately as well as in the pooled data of both trials).
Improvements in clinical status and liver parameters were also found to be greater in the nalmefene group compared with the control group. Adverse events and adverse events leading to dropout were more common with nalmefene than control. The incidence of serious adverse events was similar in control patients (3.7%) and nalmefene patients (4.5%).
Click on image to enlarge
Conclusion
As-needed Selincro was efficacious in reducing alcohol consumption in patients with a high drinking risk level at both screening and randomisation, and the effect in this subgroup was larger than in the total population of alcohol-dependent patients. Based on this finding, the authors concluded that Selincro should be offered to those alcohol-dependent patients in primary care and outpatient addiction treatment services who are not able to reduce their alcohol consumption following an initial assessment or brief intervention.
Selincro should be initiated only in patients who continue to have a high drinking risk level two weeks after initial assessment, and should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption.
Selincro is to be taken as-needed: On each day the patient perceives a risk of drinking alcohol, one tablet should be taken, preferably 1-2 hours prior to anticipated time of drinking. If the patient has started drinking alcohol without taking Selincro, the patient should take one tablet as soon as possible.
*1 standard drink = 10g of alcohol, equivalent in Irish standard to half a pint of beer, a small glass of wine, or one pub measure of spirits.
Reference:
1- van den Brink W et al. Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies. Alcohol Alcoholism 2013 Sep-Oct;48(5):570-8.