Lundbeck receives positive opinion for approval of Brintellix (vortioxetine) in the European Union

• The Committee for Medicinal Products for Human Use (CHMP) has recommended approval of Brintellix^TM for the treatment of adult patients with Major Depressive Episodes
• Major depression is a leading cause of disability and lost work productivity affecting more than 30 million people in Europe¹
• Brintellix has a unique multimodal activity profile that may translate into therapeutic benefits in depression that current therapies do not sufficiently address
• The recommended dose range is 5-20 mg per day

Valby, Denmark, 25 October 2013 - H. Lundbeck A/S (Lundbeck) today announced that the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA) adopted a positive opinion and recommended marketing authorisation of Brintellix (vortioxetine) for the treatment of adults with Major Depressive Episodes, commonly referred to as depression.

"Depression is a complex and heterogeneous disease with emotional, physical and cognitive symptoms that make it challenging for many patients to fully regain their ability to function in their personal and professional lives," said Executive Vice President Anders Gersel Pedersen, Head of Research & Development at Lundbeck. "The approval of this novel pharmacological therapy continues our long history of innovation in the research and treatment of brain diseases and underscores our commitment to advance the treatment of depression."

Brintellix has been studied in a comprehensive global clinical development program that included more than 7,000 patients.  Close to 4,000 patients were treated with Brintellix in 12 short-term (6 to 8 weeks), placebo-controlled studies of major depressive disorder. In 9 of the 12 studies, Brintellix showed statistically significant and clinically relevant effects on depression relative to placebo; one of these studies was a dedicated study in the elderly.  The symptoms of depression were assessed using the Montgomery and Åsberg Depression Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D24). In addition, significant effect was observed in the proportions of responders and remitters and in the improvement in the Clinical Global Impression – Global Improvement (CGI-I) score. The efficacy of Brintellix increased with higher doses.

Furthermore, the efficacy of Brintellix was demonstrated in patients with major depression in a 12-week head-to-head study versus the most recently approved antidepressant in the EU, agomelatine. Brintellix was significantly superior to agomelatine as measured by improvement in the MADRS total score and by the proportion of remitters and improvement in the CGI-I.

The long-term effect of Brintellix was demonstrated in a 24-64 week, relapse-prevention study. Brintellix treatment resulted in a statistically significant longer time to relapse of depression compared to placebo. Treatment with Brintellix reduced the risk of relapse by 50% compared to placebo.

The most common adverse reaction in patients treated with Brintellix was nausea. Adverse reactions were usually mild or moderate and occurred within the first two weeks of treatment. The reactions were usually transient and did not generally lead to discontinuation of therapy.

In short- and long-term clinical studies, Brintellix had no significant effect on body weight. The incidence of self-reported adverse sexual reactions was low and similar to placebo in the short- and long-term studies. In studies using the ASEX scale, no clinically relevant difference to placebo in symptoms of sexual dysfunction was seen at the 5 to 15 mg/day doses of Brintellix. For the 20 mg/day dose, an increase in TESD was seen compared to placebo. Brintellix has not been associated with any clinically significant effects on vital signs, including systolic and diastolic blood pressure and heart rate.

The recommended starting dose of Brintellix is 10 mg once daily in adults less than 65 years of age. The dose may be increased to a maximum of 20 mg once daily or decreased to a minimum of 5 mg once daily depending on individual patient response.

The European Commission usually delivers its final decision within 2-3 months of the CHMPpositive opinion. The decision will be applicable to all 28 European Union member states plus Iceland Liechtenstein and Norway. Subject to the Commission's final approval and completion of pricing and reimbursement discussions, it is expected that Brintellix will be available to patients in the first markets during the first half of 2014.

About Brintellix (vortioxetine)

The mechanism of action of vortioxetine is thought to be related to its direct modulation of serotonergic receptor activity and inhibition of the serotonin (5-HT) transporter. Nonclinical data indicate that vortioxetine is a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter, leading to modulation of neurotransmission in several systems, including predominantly the serotonin but probably also the norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate systems. This multimodal activity is considered responsible for the antidepressant and anxiolytic-like effects and the improvement of cognitive function, learning and memory observed with vortioxetine in animal studies. However, the precise contribution of the individual targets to the observed pharmacodynamic profile remains unclear and caution should be applied when extrapolating animal data directly to man.

The World Health Organization has issued a new Anatomical Therapeutic Chemical (ATC) code for Brintellix to be implemented in 2014.

Brintellix was discovered by Lundbeck researchers in Copenhagen, Denmark. Brintellix received FDA approval for the treatment of major depressive disorder on 30 September 2013.

The Science of Major Depression

The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of serotonin, norepinephrine or dopamine in the central nervous system. And while the exact cause of depression is unknown, research suggests that there are multiple serotonin receptors that may be important in major depression and may influence many biologic and neurologic processes. The release of bio-chemicals, such as serotonin, dopamine and norepinephrine enables impulses to be passed from one cell to another in the nervous system.

Lundbeck contacts

About Lundbeck

H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company specialized in brain diseases. For more than 50 years, we have been at the forefront of research within neuroscience. Our development and distribution of pioneering treatments continues to make a difference to people living with brain diseases. Our key areas of focus are alcohol dependence, Alzheimer’s disease, depression/anxiety, epilepsy, Huntington’s disease, Parkinson’s disease, schizophrenia and stroke.

Our 5,800 employees in 57 countries are engaged in the entire value chain throughout research, development, production, marketing and sales, and are committed to improving the quality of life of people living with brain diseases. Our pipeline consists of several late-stage development programs and our products are available in more 100 countries. We have research centers in China, Denmark and the United States, and production facilities in China, Denmark, France, Italy and Mexico. Lundbeck generated revenue of approximately DKK 15 billion in 2012 (EUR 2 billion; USD 2.6 billion).

Lundbeck’s shares are listed on the stock exchange in Copenhagen under the symbol ”LUN”. Lundbeck has a sponsored Level 1 ADR program listed in the US (OTC) under the symbol ”HLUYY”. For additional information, we encourage you to visit our corporate site www.lundbeck.com.

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  ¹J.Olesen, et al. Eur J Neurology. 2012; 19:155-162