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Shionogi Announces Upcoming Presentations from Symproic® (naldemedine) Studies at PAINWeek® 2018 Annual Conference

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Shionogi & Co., Ltd. (hereafter "Shionogi") will present four scientific
posters featuring pre-clinical and clinical findings of Symproic®
(naldemedine) during the 12th Annual PAINWeek® Conference,
taking place September 4-8, 2018 in Las Vegas.

Symproic is an oral tablet which functions as a peripherally acting
mu-opioid receptor antagonist medication indicated in the U.S. for the
treatment of opioid-induced constipation (OIC) in adult patients with
chronic non-cancer pain, including patients with chronic pain related to
prior cancer or its treatment who do not require frequent (e.g., weekly)
opioid dosage escalation.

Shionogi will present two clinical posters, which are integrated
analyses of the three pivotal Phase 3 studies that further demonstrated
the safety and efficacy of Symproic for the treatment of OIC in adult
patients with chronic non-cancer pain. Also presented at the conference
will be pre-clinical data which demonstrated negligible brain
penetration due to Symproic's limited ability to cross the blood brain
barrier. Additionally, there will be pre-clinical data that showed the
effect of Symproic on gastrointestinal motility with minimal impact on
the analgesic effect of opioids.

Presenters will be available at the PAINWeek Poster Session and
Reception Thursday, September 6, at 6:30-8:30 p.m. PDT.

Pre-clinical data

  • Poster #102: Mechanisms Contributing to the Low Brain
    Distribution of Naldemedine, a Peripherally Acting µ-Opioid Receptor
    Antagonist

Presenter: Ryosuke Watari

  • Poster #119: Effects of Naldemedine, a Peripherally-Acting
    µ-Opioid Receptor Antagonist, in Rat Models of Opioid-Induced
    Constipation
    Presenter: Eric Krauter

Clinical data

  • Poster #34: Effects of Naldemedine on Frequency of Spontaneous
    Bowel Movements and Associated Symptoms

Presenter: Martin Hale

  • Poster #75: Safety of Naldemedine for the Treatment of
    Opioid-Induced Constipation in Subjects with Chronic Non-Cancer Pain
    Receiving Opioid Therapy: Results of Three Global Phase 3 Clinical
    Trials
    Presenter: Lynn Webster

About Opioid-Induced Constipation (OIC)

Constipation is one of the most commonly reported side effects
associated with opioid treatment, including among patients with chronic
non-cancer pain.1 OIC is a result of increased fluid
absorption and reduced 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.2 In patients receiving opioid
therapy for chronic non-cancer pain, the prevalence of OIC ranges from
approximately 40-50 percent.3-6

About Symproic

Symproic® (naldemedine) is indicated for the treatment of OIC
in adult patients with chronic non-cancer pain, including patients with
chronic pain related to prior cancer or its treatment who do not require
frequent (e.g., weekly) opioid dosage escalation. Symproic®
was made available to patients in the US in October 2017.

Please see Important Safety Information, including Warnings &
Precautions, and Adverse Reactions below
.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Patients with known or suspected gastrointestinal (GI) obstruction and
patients at increased risk of recurrent obstruction, due to the
potential for GI perforation.

Patients with a history of a hypersensitivity reaction to Symproic.
Reactions have included bronchospasm and rash.

WARNINGS AND PRECAUTIONS

Cases of GI perforation have been reported with use of another
peripherally acting opioid antagonist in patients with conditions that
may be associated with localized or diffuse reduction of structural
integrity in the wall of the GI tract. Monitor for the development of
severe, persistent, or worsening abdominal pain; discontinue if this
symptom develops.

Symptoms consistent with opioid withdrawal, including hyperhidrosis,
chills, increased lacrimation, hot flush/flushing, pyrexia, sneezing,
feeling cold, abdominal pain, diarrhea, nausea, and vomiting have
occurred in patients treated with Symproic.

Patients having disruptions to the blood-brain barrier may be at
increased risk for opioid withdrawal or reduced analgesia. Take into
account the overall risk-benefit profile when using Symproic in such
patients. Monitor for symptoms of opioid withdrawal in such patients.

DRUG INTERACTIONS

Avoid use with strong CYP3A inducers (e.g., rifampin) because they may
reduce the efficacy of Symproic.

Use with moderate (e.g., fluconazole) and strong (e.g., itraconazole)
CYP3A inhibitors and P-glycoprotein inhibitors (e.g., cyclosporine) may
increase Symproic concentrations. Monitor for potential adverse
reactions.

Avoid use of Symproic with another opioid antagonist due to potential
for additive effect and increased risk of opioid withdrawal.

USE IN SPECIFIC POPULATIONS

Symproic crosses the placenta and may precipitate opioid withdrawal in a
fetus due to the immature fetal blood-brain barrier. Symproic should be
used during pregnancy only if the potential benefit justifies the
potential risk. Because of the potential for serious adverse reactions,
including opioid withdrawal in breastfed infants, a decision should be
made to discontinue breastfeeding or discontinue the drug, taking into
account the importance of the drug to the mother.

Avoid use in patients with severe hepatic impairment. No dose adjustment
of Symproic is required in patients with mild or moderate hepatic
impairment.

ADVERSE REACTIONS

The most common adverse reactions with Symproic as compared to placebo
in clinical trials were: abdominal pain (8% vs 2%), diarrhea (7% vs 2%),
nausea (4% vs 2%), and gastroenteritis (2% vs 1%).

In pooled Studies 1 and 2, the incidence of adverse reactions of opioid
withdrawal was 1% (8/542) for Symproic and 1% (3/546) for placebo. In
Study 3 (52-week data), the incidence was 3% (20/621) for Symproic and
1% (9/619) for placebo.

To report suspected Adverse Reactions, contact Shionogi at
1-800-849-9707 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see accompanying Full Prescribing Information including
Medication Guide for Symproic or visit 
www.symproic.com/pi.

About Shionogi

Shionogi & Co., Ltd. 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." Shionogi Inc., the
US.. based subsidiary of Shionogi & Co., Ltd., continues this focus on
the development and commercialization of high quality medicines that
protect the health and well-being of the patients we serve. The company
currently markets products in several therapeutic areas including
anti-infectives, pain, cardiovascular diseases and gastroenterology. Our
pipeline is focused on infectious disease, pain, CNS and oncology. For
more details on Shionogi Inc., visit www.shionogi.com.
For more information on Shionogi & Co., Ltd., visit www.shionogi.co.jp/en.

Forward-Looking Statements

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.

References

      1.    

Sehgal N, Colson J, Smith HS. Chronic pain treatment with
opioid analgesics: benefits versus harms of long-term therapy.
Expert Rev Neurother. 2013;13:1201-1220.

2.

Camilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe
GM. Emerging treatments in neurogastroenterology: a
multidisciplinary working group consensus statement on
opioid-induced constipation. Neurogastroenterol Motil. 2014;26:
1386-1395.

3.

Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic
noncancer pain: systematic review of efficacy and safety. Pain.
2004;112:372–80.

4.

Cook SF, Lanza L, Zhou X, et al. Gastrointestinal side effects
in chronic opioid users: results from a population based
survey.Aliment Pharmacol Ther. 2008;27(12):1224-1232.

5.

Brown RT, Zuelsdorff M, Fleming M. Adverse effects and
cognitive function among primary care patients taking opioids for
chronic nonmalignant pain. J Opioid Manag. 2006;2(3):137–146.

6.

Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioid induced
bowel disorders and narcotic bowel syndrome in patients with
chronic non-cancer pain. Neurogastroenterol Motil.
2010;22(4):424-430.

 

USSYM-0040

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