Takeda and Lundbeck announce the submission of a New Drug Application for vortioxetine, an investigational drug for the treatment of major depression, in the US

• The file is based on an extensive data package and includes statistically significant results supporting the dose range from 5-20 mg
• Major depression is among the leading causes of disability[i]. The WHO predicts depression will become the leading cause of disability by the year 2030[ii]

H. Lundbeck A/S (Lundbeck) and Takeda Pharmaceutical Company Limited (Takeda) jointly announced today the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for the investigational agent vortioxetine (formerly known as Lu AA21004) for the treatment of major depressive disorder (MDD) in adult patients.

Vortioxetine is under investigation as an antidepressant with multimodal activity that is thought to work through a combination of two mechanisms of actions: receptor activity modulation and reuptake inhibition. The NDA includes data from six short-term placebo controlled studies, including one dedicated study in the elderly. The studies have been conducted in regions throughout the world and support statistically significant efficacy of vortioxetine in a dose range of 5 to 20 mg per day. Efficacy of vortioxetine was also demonstrated in a long-term relapse-prevention study in major depression. The vortioxetine global clinical development program included more than 7,500 individuals exposed to the drug.

“The prevalence and complexity of major depressive disorder remains a growing concern for physicians and those living with the condition. This NDA submission is a critical milestone for Takeda and our partner Lundbeck, demonstrating our commitment to those living with and treating this condition,” said Azmi Nabulsi, M.D., M.P.H., president of Takeda Global Research & Development Center, Inc. “Together, we are focused on patients’ needs and believe that the multimodal activity profile of vortioxetine may translate into therapeutic benefits that help advance the treatment of depression.”

“We’re are encouraged by the results that indicate the potential for vortioxetine, if approved, to help address the needs of people suffering from major depressive disorder who are seeking additional therapeutic options,” said Anders Gersel Pedersen, Executive Vice President and Head of Research & Development at Lundbeck. “The NDA for vortioxetine represents an important step in the evaluation of a potentially new treatment option for this debilitating disease. We look forward to working with the FDA as they review the data package.”

Within 75 days of submission, the FDA is expected to determine whether the NDA filing will be accepted for review. Acceptance of the filing will trigger a milestone payment from Takeda to Lundbeck.

Takeda and Lundbeck alliance
In September 2007, Lundbeck and Takeda formed a strategic alliance for the exclusive co-development and co-commercialisation in the US 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-commercialisation of the two most advanced compounds in Lundbeck's pipeline for mood and anxiety disorders, vortioxetine and tedatioxetine (Lu AA24530). If the compounds are approved, the companies will co-promote the products in the U.S. and potentially also in 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, and further specified in connection with the announcement of the restructuring plan on 14 June 2012.

About vortioxetine
Vortioxetine is under investigation as a multimodal antidepressant that is thought to work through a combination of two mechanisms of action: receptor activity modulation and reuptake inhibition. In vitro studies indicate that vortioxetine 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 vortioxetine enhances levels of the neurotransmitters serotonin, noradrenaline, dopamine, acetylcholine and histamine in specific areas of the brain.

Across the doses of 5-20 mg the most commonly observed adverse reactions in major depression patients treated with vortioxetine in placebo-controlled studies (incidence ≥5%) were nausea and vomiting. Overall, 6.5% of the patients who received vortioxetine discontinued treatment due to an adverse reaction, compared with 3.8% of placebo-treated patients in these studies. Nausea was the most common adverse reaction reported as a reason for discontinuation and considered to be drug-related.

About major depressive disorder
Major depression is a highly prevalent, serious and debilitating medical condition and is associated with significant functional impairment and reduced quality of life[iii]. Depression is a leading worldwide cause of years lost due to disability, 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 their life-time and of these as many as two thirds will have recurrent episodes, and one third will develop a chronic condition.

While several pharmacological 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. This limited effectiveness by antidepressant treatments is multifactorial and can be explained by, among other factors, the significant clinical heterogeneity of the disease, tolerability factors and treatment adherence factors.

Both in clinical practice and clinical research the main focus in major depressive disorder has been on mood symptoms. Primary measures in clinical trials, e.g. the MADRS, reflect changes in a range of symptoms with an emphasis on mood symptoms. The disease can though be described as a complex syndrome of emotional, cognitive and somatic symptoms. The range of symptoms patients experience includes cognitive symptoms such as difficulty concentrating, forgetfulness and inability to make decisions. Persistence of cognitive symptoms in patients with major depression can contribute to impaired work function and predict poor occupational outcome.  

The tolerability of antidepressants and patients' concerns about side effects negatively affect patient outcomes. Patients with major depression 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.

Additional treatment strategies are needed to prevent and treat the common and debilitating symptoms of depression.
 

Takeda contacts 

Takeda Pharmaceutical Company Limited
Corporate Communications Dept.
+81 3 3278 2037
 

Josephine Zammuto

Corporate Communications

Takeda Global Research & Development Center , Inc.

+1 224 554 2795

Lundbeck contacts

About Takeda Pharmaceutical Company Limited
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.

About Lundbeck
H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) 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.

Safe Harbor/Forward-Looking Statements
The above information contains forward-looking statements that provide our expectations or forecasts of future events such as new product introductions, product approvals and financial performance.

Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations and it may cause any or all of our forward-looking statements here or in other publications to be wrong. Factors that may affect future results include interest rate and currency exchange rate fluctuations, delay or failure of development projects, production problems, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Lundbeck's products, introduction of competing products, Lundbeck's ability to successfully market both new and existing products, exposure to product liability and other lawsuits, changes in reimbursement rules and governmental laws and related interpretation thereof, and unexpected growth in costs and expenses.

Certain assumptions made by Lundbeck are required by Danish Securities Law for full disclosure of material corporate information. Some assumptions, including assumptions relating to sales associated with product that is prescribed for unapproved uses, are made taking into account past performances of other similar drugs for similar disease states or past performance of the same drug in other regions where the product is currently marketed. It is important to note that although physicians may, as part of their freedom to practice medicine in the US, prescribe approved drugs for any use they deem appropriate, including unapproved uses, at Lundbeck, promotion of unapproved uses is strictly prohibited.

[i] World Health Organisation; http://www.who.int/mental_health/management/depression/definition/en/

[ii] Murray CJL, Lopez AD: “The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020”.  Geneva, Switzerland; World Health Organization, 1996.

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