Shionogi Receives FDA Approval For Osphena™ (Ospemifene) For The Treatment Of Dyspareunia, A Symptom Of Vulvar And Vaginal

Shionogi Receives FDA Approval For Osphena™ (Ospemifene) For The Treatment Of
 Dyspareunia, A Symptom Of Vulvar And Vaginal Atrophy (VVA), Due To Menopause

PR Newswire

FLORHAM PARK, N.J., Feb. 26, 2013

FLORHAM PARK, N.J., Feb. 26, 2013 /PRNewswire/ --Shionogi Inc., the United
States (U.S.)-based company of Shionogi & Co., Ltd., today announced that the
U.S. Food and Drug Administration (FDA) has approved Osphena™ (ospemifene)
tablets for the treatment of moderate to severe dyspareunia (painful
intercourse), a symptom of vulvar and vaginal atrophy (VVA), due to menopause.

Osphena™, as an estrogen agonist/antagonist with tissue selective effects, is
the first and only oral treatment alternative to vaginal or oral steroidal
estrogens for women with dyspareunia due to menopause. Its biological actions
are mediated through binding to estrogen receptors, which results in
activation of estrogenic pathways in some tissues (agonism) and blockade of
estrogenic pathways in others (antagonism). The efficacy and safety of
Osphena™ was demonstrated in three clinical trials. Osphena™ demonstrated
significant improvements in dyspareunia (painful intercourse) as well as on
the physical changes of the vagina associated with menopause. These
improvements include increased superficial cells and decreased parabasal cells
and vaginal pH.

"While more than half of all women in the U.S. will experience symptoms of VVA
at some time in their postmenopausal life, the vast majority of women with VVA
are not being treated with a prescription medication because women and their
healthcare professionals are not proactively discussing the condition, and its
associated symptoms," said David J. Portman, M.D., OB/GYN and Director of the
Columbus Center for Women's Health Research. "Osphena™ received approval based
on a clinical development program in postmenopausal women with dyspareunia, a
symptom of VVA. As an oral medication taken once-daily, Osphena™ is a
convenient way for postmenopausal women to help treat dyspareunia."

"The FDA approval of Osphena™ represents an important advancement in the
treatment of dyspareunia, providing an alternative treatment option for the
millions of women living with this condition," said John Keller, Ph.D.,
President and Chief Executive Officer, Shionogi Inc. "We look forward to
building our product portfolio in women's health by advancing important
therapies, such as Osphena™."

Shionogi obtained exclusive global marketing rights to Osphena™ under a
license agreement entered into between Shionogi and QuatRx Pharmaceuticals
Company in 2010.

Osphena™ is an estrogen agonist/antagonist with tissue selective effects.
Serious risks of estrogen-alone therapy can include increased risk of
endometrial cancer, stroke, and deep vein thrombosis (DVT). Osphena™ should be
prescribed for the shortest duration consistent with treatment goals for the
individual woman. Women considering treatment for dyspareunia are encouraged
to discuss the potential risks and benefits of Osphena™ with their healthcare
provider. Pleasesee belowfor additional Important Safety Information.

Osphena™ Clinical Trials

The FDA approval of Osphena™ was supported by three Phase 3 placebo-controlled
clinical trials involving approximately 1,800 postmenopausal women with VVA
receiving either Osphena™ 60 mg (N=1102) or placebo (N=787). Two of the
clinical trials were of 12 weeks duration and the third clinical trial was a
52-week long-term safety study.

In the first and second clinical trials, Osphena™ demonstrated a statistically
significant improvement from Baseline to Week 12 in moderate to severe
dyspareunia (1st clinical trial p=0.0012, 2nd trial p<0.0001), compared to
placebo. A statistically significant increase in the proportion of superficial
cells and a corresponding statistically significant decrease in the proportion
of parabasal cells on a vaginal smear was also demonstrated (p<0.0001 for
both). The mean reduction in vaginal pH from Baseline to Week 12 was also
statistically significant (p<0.0001).

In clinical studies, the more commonly reported adverse reactions (greater
than or equal to 1 percent) in patients treated with Osphena™ 60 mg compared
to placebo were: hot flush (7.5 percent vs. 2.6 percent), vaginal discharge
(3.8 percent vs. 0.3 percent), muscle spasms (3.2 percent vs. 0.9 percent),
hyperhidrosis (1.6 percent vs. 0.6 percent), and genital discharge (1.3
percent vs. 0.1 percent).

Important Safety Information for Osphena™ (ospemifene) tablets

Boxed WARNING: Endometrial Cancer and Cardiovascular Disorders

Osphena™ is an estrogen agonist/antagonist with tissue selective effects. In
the endometrium Osphena™ has estrogen agonistic effects. There is an increased
risk of endometrial cancer in a woman with a uterus who uses unopposed
estrogen therapy. Adding a progestin to estrogen therapy has been shown to
reduce the risk of endometrial hyperplasia, which may be a precursor to
endometrial cancer. Adequate diagnostic measures, including directed or random
endometrial sampling when indicated, should be undertaken to rule out
malignancy in postmenopausal women with undiagnosed persistent or recurring
abnormal genital bleeding.

The Women's Health Initiative (WHI) estrogen-alone substudy reported an
increased risk of stroke and deep vein thrombosis (DVT) in postmenopausal
women (50 to 79 years of age) during 7.1 years of treatment with daily oral
conjugated estrogens (CE) [0.625 mg], relative to placebo. Osphena™ 60 mg had
cerebral thromboembolic and hemorrhagic stroke incidence rates of 0.72 and
1.45 per thousand women vs. 1.04 and 0 per thousand women for placebo and a
DVT incidence rate of 1.45 vs. 1.04 per thousand women for placebo. Osphena™
should be prescribed for the shortest duration consistent with treatment goals
and risks for the individual woman.

Contraindications

  oUndiagnosed abnormal genital bleeding
  oKnown or suspected estrogen-dependent neoplasia
  oActive deep vein thrombosis (DVT), pulmonary embolism (PE) or a history of
    these conditions
  oActive arterial thromboembolic disease (for example, stroke and myocardial
    infarction), or a history of these conditions
  oIn women who are or may become pregnant, as Osphena™ may cause fetal harm

Warnings and Precautions

Cardiovascular Disorders: In Osphena™ clinical trials of up to 15 months the
incidence rates compared to placebo for cerebral thromboembolic and
hemorrhagic stroke were 0.72 Osphena™ 60 mg vs. 1.04 placebo and 1.45 Osphena™
60 mg vs. 0 placebo per thousand women. Should thromboembolic or hemorrhagic
stroke occur or be suspected, Osphena™ should be discontinued immediately.

Coronary Heart Disease: In clinical trials, a single MI occurred in a woman
receiving Osphena™ 60 mg.

Venous Thromboembolism: Incidence rate of DVT was 1.45 Osphena™ vs. 1.04
placebo per thousand women. Should a VTE occur or be suspected, Osphena™
should be discontinued immediately. Osphena™ should be discontinued at least 4
to 6 weeks before surgery with increased risk of thromboembolism or during
periods of prolonged immobilization.

Malignant Neoplasms

Endometrial Cancer: Osphena™ is an estrogen agonist/antagonist with tissue
selective effects. In the endometrium Osphena™ has agonistic effects. In
Osphena™ clinical trials, no cases of endometrial cancer were seen with
exposure up to 52 weeks.

Breast Cancer: Osphena™ has not been adequately studied in women with breast
cancer; therefore Osphena™ should not be used in women with known or suspected
breast cancer or with a history of breast cancer.

Severe Hepatic Impairment: Do not use Osphena™ in women with severe hepatic
impairment as it has not been studied.

Adverse Reactions: In clinical studies, the more commonly reported adverse
reactions (greater than or equal to 1 percent) in patients treated with
Osphena™ 60 mg compared to placebo were: hot flush (7.5 percent vs. 2.6
percent), vaginal discharge (3.8 percent vs. 0.3 percent), muscle spasms (3.2
percent vs. 0.9 percent), hyperhidrosis (1.6 percent vs. 0.6 percent), and
genital discharge (1.3 percent vs. 0.1 percent).

Drug Interactions

  oDo not use estrogens or estrogen agonists/antagonists or fluconazole
    concomitantly with Osphena™.
  oCoadministration of Osphena™ with drugs that inhibit CYP3A4 and CYP2C9 may
    increase the risk of Osphena™ related adverse reactions.

Click here for Full Prescribing Information for Osphena™ (ospemifene) tablets,
including Boxed WARNING and Patient Information. For more information, please
visit www.Osphena.com.

Indications and Usage for Osphena™ (ospemifene) tablets

Osphena™ (ospemifene) is indicated for the treatment of moderate to severe
dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.

About Dyspareunia and VVA

Dyspareunia (painful intercourse) is one of the most common symptoms of vulvar
and vaginal atrophy (VVA), a chronic and progressive condition due to
menopause. Declining estrogen levels during menopause can cause tissues of the
vaginal lining to grow thinner and to lose elasticity, a condition known as
vaginal atrophy. Menopause also causes increases in vaginal pH. These changes
can lead to dyspareunia. While approximately 32 million postmenopausal women
in the U.S. experience symptoms of VVA, 93 percent are not being treated with
a prescription medication. Women who may be experiencing dyspareunia due to
menopause should consult with their healthcare professional to discuss
appropriate treatment options. Prescription therapies are often required for
symptomatic women.

About Shionogi

Shionogi Inc. is the U.S.-based subsidiary of Shionogi & Co., Ltd.,
headquartered in Osaka, Japan. Shionogi & Co., Ltd. is a major research-driven
pharmaceutical company dedicated to placing the highest value on patients.
Shionogi's research and development currently targets three therapeutic areas:
infectious diseases, pain, and metabolic syndrome. In addition, Shionogi is
engaged in new research areas such as allergy and cancer. Contributing to the
health of patients around the world through development in these therapeutic
areas is Shionogi's primary goal. For more details, please visit
www.shionogi.co.jp. For more information on Shionogi Inc., headquartered in
Florham Park, NJ, please visit www.shionogi.com.

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.

SOURCE Shionogi Inc.

Website: http://www.shionogi.com
Contact: Renee Lippman, Shionogi Inc., +1-973-307-3877, rlippman@shionogi.com;
or Amy Losak, Ketchum Public Relations, +1-646-935-3917, amy.losak@ketchum.com