Vortioxetine clinical phase III data show significant improvement in symptoms of major depression

Update: Brintellix (vortioxetine) Now FDA Approved - September 30, 2013

  • Takeda and Lundbeck present results from pivotal phase III clinical trials with vortioxetine, an investigational compound for major depression
  • First presentation of results from four pivotal clinical studies of doses of up to 20 mg/day
  • Clinical studies demonstrate efficacy at doses of 15 mg and 20 mg per day including an improvement of overall functioning
  • The safety profile was shown to be consistent with previously completed studies at lower doses

Valby, Denmark, 18 May 2013 - H. Lundbeck A/S (Lundbeck) and partner Takeda Pharmaceutical Company Limited (Takeda) today announced that the companies will be presenting new data on four pivotal studies on vortioxetine, a novel investigational drug under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of major depression.  The phase III data will be presented at the 2013 Annual Meeting of the American Psychiatric Association (APA) in San Francisco, USA.

The objective of these four studies was to evaluate the efficacy and safety profile of vortioxetine in doses ranging from 10-20 mg per day, complementing other studies in the New Drug Application (NDA) submission package that included dose ranges of 5-20 mg per day.  Three of the four pivotal studies met the primary efficacy endpoint as measured by the change from baseline of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8. Statistically significant improvements in overall symptoms of depression were demonstrated, as compared to placebo. A fourth study did not meet the primary endpoint. Results of all four studies provided additional information regarding the safety profile of vortioxetine.

"It is important that we continue to seek new options in depression because, even though there are effective treatments available, many patients remain symptomatic," said Madhukar Trivedi, M.D., professor of psychiatry, UT Southwestern Medical Center. "As a clinician, I'm encouraged by these data. They represent an important addition to the broader clinical profile for vortioxetine and support its potential as a new treatment for patients with MDD."

Dr. Trivedi, director of UT's Southwestern Depression Center, serves as scientific advisor for Lundbeck and Takeda.

About the Studies

The studies were multicenter, randomized, double-blind, parallel-group trials of adult patients taking vortioxetine designed to assess improvement in overall symptoms of depression at week 8 with vortioxetine, compared to placebo. Two studies included an established depression therapy, duloxetine, as an active reference arm. The four studies were also conducted to assess and provide further information on vortioxetine's safety profile.

A Duloxetine-referenced Fixed Dose Study Comparing Efficacy and Safety of 2 Vortioxetine Doses in the Acute Treatment of Adult MDD Patients (Study 315 conducted in the U.S.; Poster #NR9-01):

  • Vortioxetine 20 mg demonstrated significantly improved overall symptoms of MDD using the MADRS. Specifically, declines from baseline in MADRS total score ±standard error [SE] at week 8 were -12.83(±0.834), -14.30(±0.89), -15.57(±0.880), -16.90(±0.884), respectively for placebo (n=161), vortioxetine 20 mg (p=.023, n=147), and duloxetine 60 mg (p<.001, n=152) confirming assay sensitivity. Vortioxetine 15 mg did not meet statistical significance (p=NS, n=147).
  • Adverse events (AEs) reported in ≥5% of the vortioxetine group were nausea, headache, dry mouth, dizziness, diarrhea, constipation, vomiting, insomnia, fatigue, nasopharyngitis, and respiratory tract infection.

A Randomized, Double-blind, Placebo-controlled, Duloxetine-referenced Study of the Efficacy and Safety of Vortioxetine in Acute Treatment of MDD (Study 13267A conducted in Europe/South Africa; Poster #NR3-055):

  • Both 15 mg and 20 mg doses of vortioxetine were statistically significantly superior to placebo in mean change from baseline in MADRS total score at Week 8, with a mean treatment difference to placebo (n=158) of -5.6 (vortioxetine 15 mg, p<0.0001, n=148) and -7.1 points (vortioxetine 20 mg, p<0.0001, n=151).  Duloxetine (n=146) separated from placebo, confirming assay sensitivity.
  • The most commonly reported AEs (≥5%) in the vortioxetine group were nausea, headache, diarrhea, dry mouth, dizziness and hyperhidrosis.

A Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Vortioxetine 10 mg and 20 mg in Adults with Major Depressive Disorder (Study 316; Poster #NR9-06):

  • Vortioxetine 20 mg significantly improved overall symptoms of MDD. Specifically, mean declines from baseline in MADRS total score at week 8 were -10.77 (± 0.807) (n=157) for placebo and  -14.41 (±0.845) (p=0.002, n=150) for vortioxetine 20 mg. Vortioxetine 10 mg did not meet statistical difference (p=0.58, n=155).
  • The most frequently reported AEs (≥5%) in the vortioxetine group were nausea, headache, diarrhea, dizziness, constipation, vomiting, viral upper respiratory infection, and fatigue.  

A Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Two Doses of Vortioxetine in Adults with Major Depressive Disorder (Study 317; Poster #NR9-02):

  • Vortioxetine 10 mg and 15 mg did not differ significantly in improvement of overall symptoms of MDD from placebo. Specifically, mean declines from baseline in MADRS total score ±standard error [SE] at week 8 were -12.87(±1.043), -13.66(±1.064), -13.36(±1.087), respectively, for placebo (n=160), vortioxetine 10 mg (n=157) and vortioxetine 15 mg (placebo=152).
  • AEs reported by ≥5% in either vortioxetine group were nausea, headache, dry mouth, vomiting, constipation, diarrhea, dizziness and flatulence. 

The four pivotal studies presented during the meeting are part of a larger NDA data package that is currently under review by the U.S. FDA that includes data from seven positive studies — six short-term studies and one long-term maintenance study — conducted in regions throughout the world. The vortioxetine global clinical program evaluated the effectiveness and safety profile of vortioxetine in a broad dose range of 5-20 mg per day and included more than 7,500 total subjects.

About vortioxetine

Vortioxetine (currently under review with the FDA) is an investigational antidepressant with multimodal activity that is thought to work through a combination of two mechanisms of action: receptor activity modulations and reuptake inhibition.

In vitro studies 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 serotonin (5-HT) 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 5-20mg, the most commonly observed adverse reactions in MDD patients treated with vortioxetine in placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) were: nausea, constipation 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 (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, cognitive 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 treatmentsi).

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.

MDD is the 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.

Depression is associated with significant functional impairment and reduced quality of life .  Many patients experience a range of symptoms of the disease that include cognitive symptoms such as difficulty concentrating, forgetfulness and inability to 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.

Lundbeck contacts

 

Investors: Media:
   
Palle Holm Olesen Mads Kronborg
Chief Specialist, Head of Investor Relations Media Relations Manager
PALO@lundbeck.com MAVK@lundbeck.com
+45 36 43 24 26 +45 36 43 28 51
   
     
Jens Høyer  
Investor Relations Officer
JSHR@lundbeck.com
 
+45 36 43 33 86  

About Lundbeck

Lundbeck is a global pharmaceutical company highly committed to improving the quality of life of people living with brain diseases. For this purpose, Lundbeck is engaged in the entire value chain throughout research, development, production, marketing and sales of pharmaceuticals across the world. The company's products are targeted at disorders such as depression and anxiety, psychotic disorders, epilepsy, Huntington's, Alzheimer's and Parkinson's diseases. Lundbeck's pipeline consists of several mid- to late- stage development programs.

Lundbeck employs more than 5,800 people worldwide, 2,000 of whom are based in Denmark. We have employees in 57 countries, and our products are registered in more than 100 countries. We have research centers in Denmark, China and the United States and production facilities in Italy, France, Mexico, China and Denmark. Lundbeck generated revenue of approximately DKK 15 billion in 2012. Lundbeck's shares are listed on the stock exchange in Copenhagen under the symbol "LUN". Lundbeck has a sponsored Level 1 ADR programme listed in the US (OTC) under the symbol "HLUYY". For additional information, we encourage you to visit our corporate site 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.

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1 Rush et al; Am J Psych 2006; 163: 1905-1917

Posted: May 2013

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