Selincro® (nalmefene): Changing the treatment of alcohol dependence

Our commercial product Selincro (nalmefene) is an orally administered opioid receptor ligand for the treatment of alcohol dependence.

Selincro is approved in Europe for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high level of alcohol consumption.

Unlike other treatments for this disease, Selincro is taken on an ‘as needed’ basis to reduce the desire to drink, thus offering patients a novel treatment option compared to traditional methods which are aimed at total abstinence and usually include intensive psychosocial therapy. Biotie has licensed global development and commercialization rights to nalmefene to H. Lundbeck A/S, a leader in CNS drug development.

About alcohol dependence

Alcohol dependence is a brain disease with a high probability of following a progressive course1,2.  Alcohol is toxic to most organs of the body, and the level of consumption is strongly correlated with the risk for long-term morbidity and mortality3. Alcohol is a causal factor in more than 60 types of disease and injury4. Genetic and environmental factors are important in the development of alcohol dependence; genetic factors account for an estimated 60% of the risk of developing the disease5. A central characteristic of alcohol dependence is the often overpowering desire to consume alcohol. Patients experience difficulties in controlling the consumption of alcohol and continue consuming alcohol despite harmful consequence6.

Excessive alcohol consumption is common in many parts of the world, especially in Europe where more than 14 million people are alcohol dependent3,7. In Europe the treatment gap is very large, with only 8% of patients receiving any treatment.8 Both abstinence and reduction goals should be considered as part of a comprehensive treatment approach for patients with alcohol dependence9.

Selincro product profile

Selincro is a small molecule opioid receptor modulator that inhibits the reward pathway in the brain that reinforces the desire and craving for alcohol and other addictive substances. As a result, Selincro targets a novel principle in the treatment of alcohol dependence by removing a person’s desire to drink.

Selincro builds on a novel principle of treating alcohol dependence. Unlike existing therapies, treatment with Selincro is not aimed at keeping the patients from drinking. Instead, Selincro helps to control and limit the intake of alcohol. Selincro distinguishes itself by being available as a tablet formulation to be taken only according to need, ("as needed"), whereas existing pharmaceuticals must be taken continuously over a longer period of time and are aimed at maintaining abstinence.

Selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (>60 g/day for men, >40 g/day for women) without physical withdrawal symptoms and who do not require immediate detoxification.  Selincro should be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and the reduction of alcohol consumption. Treatment should be initiated only in patients who continue to have a high drinking risk level two weeks after an initial assessment.  Selincro is to be taken as-needed; that is, on each day the patient perceives a risk of drinking alcohol, one tablet should be taken, preferably 1-2 hours prior to the anticipated time of drinking.

Collaboration partner

Biotie has licensed global development and commercialization rights to nalmefene to Danish CNS specialist, H. Lundbeck A/S (Lundbeck).  Lundbeck is an ideal partner for Biotie, as it has significant experience and a substantial track record in depression, a therapeutic area with many parallels to alcohol use disorders.  Lundbeck’s specialist marketing force and its long-established relationships with prescribers in the relevant therapeutic areas will be important in driving a successful launch and maximizing the market potential for nalmefene.

Under the terms of the agreement with Lundbeck, Biotie is eligible for up to EUR 94 million in upfront and milestone payments plus royalties on sales.

About the clinical studies with Selincro

For the approval of Selincro, efficacy was assessed in patients with a high drinking risk level (defined by WHO: men > 60 gram per day, women >40 gram per day (1 standard drink ~ 10 grams of alcohol)). Patients enrolled in the studies with high drinking risk level drank on average 10.5 standard drinks per day (equivalent to approximately 1.5 bottles of wine). Patients treated with Selincro showed a more than 40% reduction in total alcohol consumption within the first month, and at study end (6 or 12 months) the alcohol intake was reduced by more than 60%. This corresponds to an average reduction equal to nearly one bottle of wine per day. The reduction of alcohol consumption in patients with high drinking risk level was significantly better than placebo at study end in all three studies and considered clinically relevant. Data from the 1-year study suggested longer term efficacy of Selincro beyond 6 months and up to 1 year of treatment. There were no major safety concerns identified during the studies, and Selincro was generally well tolerated.

Program status

In February 2013 Biotie´s partner Lundbeck received European marketing authorization from the European Commission for Selincro for the reduction of alcohol consumption in adult patients with alcohol dependence who have high level of alcohol consumption. The product has since been introduced in Europe, and favorable reimbursement decisions were made in the second half of 2014 in a number of key markets, including France, Spain and the United Kingdom.

Lundbeck and Otsuka Pharmaceutical Co. Ltd. are collaborating, as part of their existing alliance, to develop and commercialize nalmefene in Japan, and a 660-patient Phase 3 study in Japan was commenced in Q1 2015.

Scientific literature related to the project

Mann K, Bladström A, Torup L, Gual A, van den Brink W. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry. 2013 Apr 15;73(8):706-13. doi: 10.1016/j.biopsych.2012.10.020. Epub 2012 Dec 11. To purchase this paper click here

Gual A, He Y, Torup L, van den Brink W, Mann K, ESENSE 2 Study Group. A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol. 2013 Nov;23(11):1432-42. doi: 10.1016/j.euroneuro.2013.02.006. Epub 2013 Apr 3. To purchase this paper click here

van den Brink W, Aubin HJ, Bladström A, Torup L, Gual A, Mann K.
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 Alcohol. 2013 Sep-Oct;48(5):570-8. doi: 10.1093/alcalc/agt061. Epub 2013 Jul 19. Available here

van den Brink W, Sørensen P, Torup L, Mann K, Gual A, for the SENSE Study Group. Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: A 1-year, randomised controlled study. J Psychopharmacol. 2014 Mar 26;28(8):733-744. [Epub ahead of print] Available here

van den Brink W, Strang J, Gual A, Sørensen P, Jensen TJ, Mann K. Safety and tolerability of as-needed nalmefene in the treatment of alcohol dependence: results from the Phase III clinical programme. Expert Opin Drug Saf. 2015 Apr;14(4):495-504. doi: 10.1517/14740338.2015.1011619. Epub 2015 Feb 4. To purchase this paper click here

Karhuvaara S, Simojoki K, Virta A, Rosberg M, Löyttyniemi E, Nurminen T, Kallio A, Mäkelä R. Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study. Alcohol Clin Exp Res. 2007 Jul;31(7):1179-87. Epub 2007 Apr 19. To purchase this paper click here

Soyka M. Nalmefene for the treatment of alcohol dependence: a current update. Int J Neuropsychopharmacol. 2014 Apr;17(4):675-84. doi: 10.1017/S1461145713001284. Epub 2013 Nov 18.
Available here


References:

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  2. Leshner. Science 1997; 278: 45-47
  3. Rehm et al. Eur Addict Res 2003; 9: 147-156
  4. WHO. Global status report on alcohol and health, 2011
  5. Schuckit. Ch. 98. In: Davis et al (eds). Neuropsychopharmacology: The Fifth Generation of Progress. 2002
  6. WHO, ICD-10, F10-19
  7. Wittchen et al. Eur Neuropsychopharmacol 2011;21(9): 655-679
  8. Kohn et al. Bull World Health Organ 2004; 82(11):858-866
  9. Ambrogne. J Subst Abuse Treat 2002; 22(1): 45-53
Updated 17 November, 2015