Shionogi Concludes a Contract for the Commercialization of Rizmoic® (naldemedine), an Opioid-Induced Constipation Therapeutic Agent, in Germany, the UK, and the Netherlands

OSAKA, Japan & AMSTERDAM–(BUSINESS WIRE)–Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President & CEO: Isao
Teshirogi, Ph.D.; hereafter “Shionogi”) announced today that Shionogi
concluded a distribution contract with Sandoz (Headquarters:
Holzkirchen, Germany; CEO a.i: Francesco Balestrieri hereinafter
“Sandoz”) for the sale of Rizmoic® (naldemedine) for the treatment of
opioid-induced constipation (OIC) in adult patients previously treated
with a laxative in the key European markets of Germany, the UK, and the
Netherlands, plus right of first refusal for certain other European
markets.

Sandoz has a strong presence in the European market for opioid
analgesics, as well as a complementary strategic focus on innovative
therapeutic alternatives to combat opioid dependency. According to this
contract, Sandoz will commercialize Rizmoic® in Germany, the UK, and the
Netherlands, and Shionogi will be responsible for its manufacturing and
development. Dr. John Keller, Chief Executive Officer of Shionogi B.V.,
the subsidiary of Shionogi in Europe, said “Through this contract, we
are able to bring together Sandoz’s commercial expertise in Europe,
particularly in the field of opioid analgesics with the OIC treatment
know-how of Shionogi, which has been developing naldemedine globally. We
therefore expect Rizmoic® to contribute significantly to OIC treatment
in clinical settings in European countries in the future.”

On February 22, 2019, the European Commission (EC) granted the Marketing
Authorization (MA) for Rizmoic® for the treatment of OIC in adult
patients who have previously been treated with a laxative.^{1, 2}
Rizmoic® is planned to be launched in Germany and the UK in 2019 and in
the Netherlands in 2020. Rizmoic® was launched under the brand name
Symproic® in Japan in June 2017, and in the United States in October
2017.^3,4 Shionogi plans to initiate a clinical study of
naldemedine in paediatric patients with OIC in EU, in accordance with an
agreed paediatric investigation plan, as well as a clinical study in
adult patients with post-operative ileus.

Shionogi’s research and development efforts target pain/central nervous
system (CNS) as one of its priority areas in the mid-term business plan,
SGS2020, in which Shionogi has positioned “Grow sustainably as a drug
discovery-based pharmaceutical company contributing to a more vigorous
society through improved healthcare” as its vision. Shionogi constantly
strives to improve the quality of life of patients who suffer from pain
or side effects of analgesics by bringing forth innovative drugs.

About Opioid-induced Constipation

Constipation is one of the most commonly reported side effects
associated with opioid treatment, particularly among patients with
chronic non-cancer pain and patients with cancer pain.⁵ OIC
is a result of increased fluid absorption and reduced gastro-intestinal
(GI) motility due to mu-opioid receptor binding in the GI tract. OIC is
defined as a change in bowel habits that is characterized by any of the
following after initiating opioid therapy: reduced bowel movement
frequency, development or worsening of straining to pass bowel
movements, a sense of incomplete rectal evacuation, or harder stool
consistency.⁶ In patients receiving opioid therapy for
chronic non-cancer pain, the prevalence of OIC ranges from approximately
40-60 percent.⁷

About Rizmoic®

Rizmoic® (naldemedine) is indicated for the treatment of opioid-induced
constipation (OIC) in adult patients who have previously been treated
with a laxative. Rizmoic® is a peripherally acting mu-opioid receptor
antagonist (PAMORA) that has been developed by Shionogi as a once-daily
treatment of OIC. The efficacy and safety of naldemedine have been
evaluated in randomized, double-blinded, placebo-controlled studies in
adult patients with OIC who have chronic non-cancer pain or who have
cancer pain.^8-12 Rizmoic® is expected to be a new treatment
option that can improve the quality of life significantly in patients
with OIC in pain management with opioid analgesics.

About Shionogi

Shionogi & Co., Ltd. (“Shionogi”) is a Japanese major research-driven
pharmaceutical company dedicated to bringing benefits to patients based
on its corporate philosophy of “supplying the best possible medicine to
protect the health and wellbeing of the patients we serve.” The company
currently markets products in several therapeutic areas including
anti-infectives, pain, CNS disorders and gastroenterology. Shionogi’s
research and development currently target two therapeutic areas:
infectious diseases and pain/CNS disorders. For more information on
Shionogi, please visit http://www.shionogi.co.jp/en/.
Shionogi B.V. is the European subsidiary of Shionogi & Co., Ltd. based
in Amsterdam, Netherlands. For more information on Shionogi B.V. please
visit http://www.shionogi.eu/.

Forward Looking Statement

This announcement contains forward-looking statements. These
statements are based on expectations in light of the information
currently available, assumptions that are subject to risks and
uncertainties which could cause actual results to differ materially from
these statements. Risks and uncertainties include general domestic and
international economic conditions such as general industry and market
conditions, and changes of interest rate and currency exchange rate.
These risks and uncertainties particularly apply with respect to
product-related forward-looking statements. Product risks and
uncertainties include, but are not limited to, completion and
discontinuation of clinical trials; obtaining regulatory approvals;
claims and concerns about product safety and efficacy; technological
advances; adverse outcome of important litigation; domestic and foreign
healthcare reforms and changes of laws and regulations. Also for
existing products, there are manufacturing and marketing risks, which
include, but are not limited to, inability to build production capacity
to meet demand, unavailability of raw materials and entry of competitive
products. The company disclaims any intention or obligation to update or
revise any forward-looking statements whether as a result of new
information, future events or otherwise.

Reference

^1. Release on February 22, 2019

Shionogi announces European Union Marketing Authorisation for Rizmoic®
(naldemedine) for the treatment of opioid-induced constipation in adults
previously treated with a laxative

^2. SmPC, Rizmoic®, Shionogi, Feb 2019

^3. Release on June 7, 2017

Opioid-Induced Constipation therapeutic agent ‘Symproic® (naldemedine)
Tablets 0.2mg’ launched in Japan

^4. Release on October 12, 2017

Shionogi Inc. and Purdue Pharma L.P. Announce U.S. Availability of
Symproic® (naldemedine) for the Treatment of Opioid-Induced Constipation
in Adults with Chronic Non-Cancer Pain

^5. Sehgal N, et al. Chronic pain treatment with opioid
analgesics benefits versus harms of long-term therapy. Expert Rev
Neurother. 2013;13:1201-1220.

^6. Camilleri M, et al. Emerging treatments in
neurogastroenterology: a multidisciplinary working group consensus
statement on opioid-induced constipation. Neurogastroenterol Motil.
2014;26: 1386-1395.

^7. Coyne E, et al. Opioid-Induced constipation among patients
with chronic Noncancer pain in the United States, Canada, Germany and
the United Kingdom: Laxative use, response and symptom burden over time.
Pain. 2015;16:1551–1565.

^8. Hale M, et al. Naldemedine versus placebo for
opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre,
phase3, double-blind, randomised, parallel-group trials. Lancet
Gastroenterol Hepatol. 2017. Published online May 30, 2017.

^9. Webster L, et al. Long term use of naldemedine in the
treatment of opioid-induced constipation in patients with chronic
noncancer pain: a randomized, double-blind, placebo-controlled phase 3
study. Pain. 2018. Published online February 6 2018.

^10. Bowers B, et al. The evolving role of long-term
pharmacotherapy for opioid-induced constipation in patients being
treated for noncancer pain. Jour Pharm Practice. 2017.

^11. Katakami N, et al. Randomized phase III and extension
studies: efficacy and impacts on quality of life of naldemedine in
subjects with opioid-induced constipation and cancer. Ann Oncol. 2018.
Published online Apr 18, 2018.

^12. Satomi E, et al. Efficacy and tolerability of naldemedine
in patient with cancer and opioidinduced constipation: A pooled subgroup
analysis of 2 randomised placebo-controlled studies. Ann Oncol. 2018. 29
(suppl 8).

Contacts

Shionogi Europe
Dr. Mark Hill, Shionogi, [email protected]
Mirjam
Korn, Shionogi, [email protected]

Shionogi & Co., Ltd.
Corporate Communications Department
Telephone:
+81-6-6209-7885