Statistically significant clinical phase III results of Lu AA21004 provide basis for submission of an NDA and MAA for major depression (MDD)

• New clinical phase III data demonstrate the efficacy of the investigational compound Lu AA21004 compared to placebo in the treatment of MDD seen in several previous studies
• Data from six out of eight short-term placebo controlled studies so far in the pivotal programme, conducted in regions throughout the world have established and repeated statistically significant efficacy of Lu AA21004 in a dose range from 5 to 20mg
• Efficacy of Lu AA21004 is further confirmed in a positive trial in an elderly population, and in a long-term relapse-prevention study in MDD
• Based on the current data package Lundbeck and its partner Takeda intend to submit Lu AA21004 for US registration during the second half of 2012. Separately, Lundbeck plans to submit for the European and Canadian registration during the second half of 2012
• Lu AA21004 is under investigation as a novel multimodal anti-depressant which offers the possibility to target several transmitter systems with a single molecule

H. Lundbeck A/S (Lundbeck) today announced positive top-line results from three recently completed phase III clinical studies of Lu AA21004, an investigational drug for the treatment of adults with major depressive disorder (MDD) using dosages from 10 to 20mg.

Two studies were conducted exclusively in the US and one study was primarily conducted in Europe. The positive results from these three studies showed that Lu AA21004 statistically significantly reduced depression symptoms in patients with MDD compared to placebo as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). In total, out of the ten large, placebo-controlled studies of Lu AA21004 completed in patients with MDD, eight have shown effect of Lu AA21004. Further analysis of the data is ongoing and data are expected to be presented at upcoming medical conferences.

Lu AA21004 was generally well-tolerated in the three phase III studies, thereby confirming previous findings at lower doses. The most common adverse events (AE) observed in the Lu AA21004 group were nausea, headache, diarrhea and vomiting.

Based on the current data, Lundbeck and its partner Takeda plan to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) during the second half of 2012. Separately, Lundbeck plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) and to Health Canada for Lu AA21004 during the second half of this year as well.

"We are very pleased with the consistency of the efficacy and tolerability profile across the programme that we have obtained so far and we plan to file for registration for regulatory approval for Lu AA21004 in both the US and Europe in the second half of 2012" says Executive Vice President Anders Gersel Pedersen, Head of Research & Development at Lundbeck.

Around 5,000 individuals have been exposed to Lu AA21004 in the US and around the world across the clinical trial programme. Statistically significant results have now been established in MDD on all doses from 5-20mg in these studies.

Lundbeck and its partner Takeda are also committed to further investigating the tolerability of Lu AA21004 and its effects on cognitive dysfunction in depression.

Conference call details
At 9.00 CET 15 May 2012, a conference call will be held. Investors will be able to listen in via a link on www.lundbeck.com, which can be found under ‘Investors’. Presentation material for the conference call will be made available approximately one hour before on the same page.

About the clinical phase III studies
The three studies were randomized, double-blind, placebo-controlled, fixed-dose studies evaluating the efficacy, safety and tolerability of Lu AA21004 in adult individuals with MDD.

In one of the US studies, a total of 614 participants were randomized to receive Lu AA21004 15 mg or 20 mg, or duloxetine 60 mg (used as a positive reference compound), or placebo, once-daily. The other US trial included 462 subjects and compared 10 mg and 20mg of Lu AA21004 to placebo, once daily. In the European study 600 subjects, men and women 18-75 years of age were randomized to receive Lu AA21004 15 and/or 20 mg once daily.

All patients participating in the study met the criteria for MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR).

About Lu AA21004
Lu AA21004 is under investigation as a multimodal anti-depressant that is thought to work through a combination of two complementary mechanisms of action: receptor activity modulation and reuptake inhibition.  In vitro studies indicate that Lu AA21004 is a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the serotonin transporter (SERT). In vivo non-clinical studies have demonstrated that Lu AA21004 modulates neuronal firing and neurotransmitter release in multiple systems, resulting in enhanced levels of serotonin, noradrenaline, dopamine, acetylcholine and histamine in specific areas of the brain.

The multimodal activity profile of Lu AA21004 may translate into therapeutic benefits in depression that current therapies do not sufficiently address.

About major depressive disorder (MDD)
Major depressive disorder (MDD) - commonly referred to as major depression – is a highly prevalent, serious and debilitating medical condition. The disease can be described as a complex syndrome of emotional, psychological and somatic symptoms.

The significant clinical heterogeneity of the disease is frequently cited as a reason for the limited efficacy of currently available antidepressants. While several treatments are available, around 50% of patients remain symptomatic following first-line treatment, and a third fail to achieve full resolution of depressive symptoms after four established treatments.

MDD is the leading cause of years lost due to disability in the world, and projected to be the biggest contributor to the worldwide burden of disease by 2030. It is estimated that between a quarter and a third of the population will develop at least one episode of major depression during life-time and of these as many as two thirds will have recurrent episodes, and one third will develop a chronic condition.

Depression is associated with significant functional impairment and reduced quality of life[i] .  Many patients experience a range of symptoms of the disease that include cognitive symptoms such as the ability to think, concentrate, learn, remember and make decisions). Persistence of cognitive symptoms in patients with MDD can contribute to impaired work function and predict poor occupational outcome. Additional treatment strategies are needed to prevent and treat these common and debilitating symptoms of depression.

The tolerability of antidepressants and patients’ concerns about side effects negatively affect patient outcomes. Patients with MDD who experience at least one severe side effect are twice as likely to discontinue treatment prematurely. Common reasons for premature treatment discontinuation include weight gain, and gastrointestinal and sexual side effects.

Takeda and Lundbeck alliance
In September 2007, Lundbeck and Takeda formed a strategic alliance for the exclusive co-development and co-commercialization in the United States and Japan of several compounds in Lundbeck's pipeline for the treatment of mood and anxiety disorders. The partnership initially focuses on co-development and co-commercialization of the two most advanced compounds in Lundbeck's pipeline for mood and anxiety disorders, Lu AA21004 and Lu AA24530. Once approved, the companies plan to co-promote the products in the United States and Japan.

Financial guidance
The content of this release will have no influence on the Lundbeck Group's financial guidance for 2012 which was provided on 8 February 2012 in connection with the release of the financial results for 2011.

Lundbeck contacts

About Lundbeck
H. Lundbeck A/S (LUN.CO, LUN DC, HLUKY) is an international pharmaceutical company highly committed to improving the quality of life for people suffering from brain disorders. For this purpose, Lundbeck is engaged in the research, development, production, marketing and sale of pharmaceuticals across the world. The company’s products are targeted at disorders such as depression and anxiety, psychotic disorders, epilepsy and Huntington’s, Alzheimer’s and Parkinson’s diseases.

Lundbeck was founded in 1915 by Hans Lundbeck in Copenhagen, Denmark. Today Lundbeck employs approximately 6,000 people worldwide. Lundbeck is one of the world’s leading pharmaceutical companies working with brain disorders. In 2011, the company's revenue was DKK 16.0 billion (approximately EUR 2.1 billion or USD 3.0 billion). For more information, please visit www.lundbeck.com.

[i] Tracy L. Greer et al.: ”Defining and Measuring Functional Recovery from Depression”; CNS Drugs 2010; 24 (4): 264-284