Takeda And Lundbeck Present Results From Pivotal Phase 3 Clinical Trials With
Vortioxetine, An Investigational Compound For Major Depressive Disorder
Results Presented at 166th Annual American Psychiatric Association Meeting
SAN FRANCISCO, May 18, 2013
SAN FRANCISCO, May 18, 2013 /PRNewswire/ --Takeda Pharmaceutical Company
Limited (Takeda) and H. Lundbeck A/S (Lundbeck) today announced that the
companies will be presenting new data from four studies that evaluated
effectiveness in treating the overall symptoms of depression in patients
taking vortioxetine, an investigational agent under review with the U.S. Food
and Drug Administration (FDA) for the treatment of major depressive disorder
(MDD). These data will be presented at the 2013 American Psychiatric
Association Annual Meeting (APA) in San Francisco.
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-Asberg 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 living
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 that validated the studies and confirmed "assay
sensitivity." 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):
oVortioxetine 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),
-15.57(+/-0.880), ‑16.90(+/-0.884), respectively for placebo (n=161),
vortioxetine 20 mg (p=0.023, n=147), and duloxetine 60 mg (p<0.001, n=152)
confirming assay sensitivity. Vortioxetine 15 mg did not meet statistical
significance (p=NS, n=147).
oAdverse 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):
oBoth 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.
oThe 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):
oVortioxetine 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).
oThe 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):
oVortioxetine 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
oAEs 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.
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
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 percent of the patients who received
vortioxetine discontinued treatment due to an adverse reaction, compared with
3.8 percent 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.
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's U.S. business is based in
Deerfield, Illinois. To learn more about Lundbeck in the U.S., visit
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.
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 Takeda Pharmaceuticals U.S.A., Inc. and Takeda Global Research &
Development Center, Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals U.S.A., Inc. and Takeda
Global Research & Development Center, Inc. are subsidiaries of Takeda
Pharmaceutical Company Limited, the largest pharmaceutical company in Japan.
The respective companies currently market oral diabetes, insomnia,
rheumatology, gastroenterology and cardiovascular disease treatments and seek
to bring innovative products to patients through a pipeline that includes
compounds in development for diabetes, gastroenterology, neurology and other
conditions. To learn more about these Takeda companies, visit www.takeda.us.
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SOURCE Takeda Pharmaceutical Company Limited; Lundbeck
Contact: Ashleigh Duchene, Public Affairs, Lundbeck LLC, 847-282-1164, or
Palle Holm Olesen, Chief Specialist, Head of Investor Relations, H. Lundbeck
A/S, email@example.com, +45 36 43 24 26, or Jessica Tuquero, Corporate
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