Health Canada Approves Otsuka and Lundbeck's REXULTI™ (brexpiprazole) as a Treatment for Schizophrenia in Adults

TOKYO & MONTREAL–(BUSINESS WIRE)–Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Lundbeck Canada announce
that Health Canada issued a Notice of Compliance for
REXULTI™ (brexpiprazole) for the treatment of schizophrenia in adults.
REXULTI™ was discovered by Otsuka and co-developed with Lundbeck. It
will be co-marketed by the two companies and is expected to become
commercially available in Canada this spring.

REXULTI™ was studied in more than 2700 subjects with schizophrenia in
phase II and III clinical trials, and the approval was supported by
three completed placebo-controlled clinical phase III studies in the
now-approved indication. In clinical trials, REXULTI™ was found to
significantly improve both positive and negative symptoms.1,2,3

The efficacy, safety and tolerability of REXULTI™ was established in two
6-week, fixed-dose, phase III randomized, placebo-controlled clinical
trials and one 52-week randomized withdrawal trial in subjects with
schizophrenia who were experiencing an acute exacerbation of psychotic
symptoms.1,2,3

“Brexpiprazole, a new treatment option for schizophrenia, with a
unique mechanism of action provides us with new hope for patients
suffering from this devastating illness,” said Dr Ofer Agid, associate
professor of psychiatry, Schizophrenia Program, Center for Addiction and
Mental Health (CAMH), Department of Psychiatry, University of Toronto,
Toronto, Ontario.

Schizophrenia is a severely debilitating and progressive mental illness4
affecting approximately 1% of the Canadian population—more than 350,000
Canadians.5,6,7

“It is always exciting to have a new treatment option for patients
with schizophrenia since this is an illness where there are still
patients who are not able to achieve remission”, says Chris Summerville,
CEO of the Schizophrenia Society of Canada.

Due to the underlying heterogeneity in the manifestations of
schizophrenia, and differences in patient tolerability and response to
treatment, patients are in need of additional treatment options.

“Psychiatric diseases remain a challenging therapeutic area where
many people are unsatisfied with their treatments,” noted Allison
Rosenthal, general manager of Otsuka Canada Pharmaceutical Inc. “Today’s
approval of REXULTI is another example of Otsuka and Lundbeck’s
commitment to bringing new therapeutic alternatives to the mental health
community.”

“All treatment options require healthcare providers, patients and
caregivers to balance efficacy and tolerability in managing their
diseases,” said Sylvie Pilon, vice president and general manager,
Lundbeck Canada. “We are proud to introduce REXULTI to help adult
patients living with schizophrenia.”

REXULTI™ is given in a once-daily oral dose with a well-defined
titration schedule that can be taken with or without food.8

About REXULTI™

REXULTI™ (brexpiprazole) is a new molecule (i.e., not a metabolite or
isomer) discovered by Otsuka and co-developed by Otsuka and Lundbeck.
The mechanism of action for REXULTI™ in the treatment of schizophrenia
is unknown. However, the efficacy of REXULTI™ may be mediated through a
combination of partial agonist activity at serotonin 5-HT1A and dopamine
D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. In
addition, REXULTI™ exhibits high affinity (subnanomolar) for these
receptors as well as for noradrenaline alpha1B/2C receptors.9

About Otsuka

Otsuka Pharmaceutical Co., Ltd., is a global healthcare company with the
corporate philosophy: “Otsuka – people creating new products for better
health worldwide”. Otsuka researches, develops, manufactures and markets
innovative and original products, with a focus on pharmaceutical
products for the treatment of diseases and nutraceutical products for
the maintenance of everyday health.

Otsuka Canada Pharmaceutical Inc. (OCPI) is an innovative, fast-growing
health care company that commercializes Otsuka medicines in Canada. OCPI
aims to improve the quality of life and health of patients through its
commitments to neuroscience, cardiovascular health, oncology and
nephrology. OCPI was established in 2010, with headquarters
in Saint-Laurent, Quebec.

OCPI is part of Otsuka Pharmaceutical Co., Ltd., a wholly owned
subsidiary of Otsuka Holdings Co., Ltd., based in Tokyo, Japan. Otsuka
Holdings had consolidated sales of approximately USD 11 billion in 2016.
Otsuka welcomes you to visit its global pharmaceutical website at https://www.otsuka.co.jp/en
and the website of OCPI at http://otsukacanada.com.

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, Lundbeck
has been at the forefront of research within neuroscience. Lundbeck’s
development and distribution of pioneering treatments continues to make
a difference to people living with brain diseases. The key areas of
focus are Alzheimer’s disease, depression/anxiety, Parkinson’s disease
and schizophrenia. Lundbeck’s 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. The Lundbeck pipeline consists of
several late-stage development programs and products are available in
more than 100 countries. Lundbeck has 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 15.6 billion in 2016 (EUR 2.0 billion; USD 2.2 billion).

A division of Denmark-based H. Lundbeck A/S, Lundbeck Canada Inc. has
been a trusted source of innovative new treatments for Canadians since
1995 with headquarters in Montreal. Originally focused on providing
products for the treatment of diseases such as depression, anxiety,
Alzheimer’s disease and schizophrenia, Lundbeck Canada also offers new
cancer therapies for the treatment of chronic lymphocytic leukemia and
non-Hodgkin lymphoma. A patient-focused partner in Canadian health care,
Lundbeck Canada’s mission is to improve the quality of life for people
living with brain diseases and cancer.

REXULTI™ is a trademark of Otsuka Pharmaceutical Co., Ltd., used under
license by Otsuka Canada Pharmaceutical Inc.

REFERENCES

1. Kane JM, Skuban A, Ouyang J, Hobart M, Pfister S et al. (2015) A
multicenter, randomized, double-blind, controlled phase 3 trial of
fixed-dose brexpiprazole for the treatment of adults with acute
schizophrenia. Schizophr Res 164 (1-3): 127-135.

2. Correll CU, Skuban A, Ouyang J, Hobart M, Pfister S et al. (2015)
Efficacy and safety of brexpiprazole for the treatment of acute
schizophrenia: A 6-Week randomized, double-blind, placebo-controlled
trial. Am J Psychiatry 172 (9): 870-880.

3. Fleischhacker WW, Hobart M, Ouyang J, Forbes A, Pfister S et al.
(2016) Efficacy and safety of brexpiprazole (OPC-34712) as maintenance
treatment in adults with schizophrenia: a randomized, double-blind,
placebo-controlled study. Int J Neuropsychopharmacology (2017) 20(1):
11-21.

4. American Psychiatric Association (2013) Diagnostic and Statistical
Manual of Mental Disorders. 5th Ed. Arlington, VA: American Psychiatric
Association.

5. Mueser KT, McGurk SR. Schizophrenia. Lancet 2004;363:2063-72.

6. Goeree R, Farahati F, Burke N, Blackhouse G, O’Reilly D et al.
(2005) The economic burden of schizophrenia in Canada in 2004. Curr Med
Res Opin 21 (12): 2017-2028.

7. Mood Disorders Society of Canada. Quick facts on mental illness
and addictions in Canada, 3rd Edition, Nov 2009. (Accessed December 19,
2016, at https://mdsc.ca/quick-facts/.)

8. Otsuka Canada Pharmaceutical Inc. REXULTITM (brexpiprazole)
product monograph. February 16, 2017.

9. Maeda, K. et al. Pharmacological profile of brexpiprazole
(OPC-2471234712): a novel serotonin-dopamine activity modulator. Poster
presentation at American Psychiatric Association annual meeting, May
3-7, 2014.