Takeda Receives FDA Approval for Three New Type 2 Diabetes Therapies, NESINA (alogliptin) and Fixed-Dose Combinations OSENI

 Takeda Receives FDA Approval for Three New Type 2 Diabetes Therapies, NESINA
 (alogliptin) and Fixed-Dose Combinations OSENI (alogliptin and pioglitazone)
                  and KAZANO (alogliptin and metformin HCl)

  PR Newswire

  DEERFIELD, Illinois and OSAKA, Japan, Jan. 28, 2013

DEERFIELD, Illinois and OSAKA, Japan, Jan. 28, 2013 /PRNewswire/ -- Takeda
Pharmaceutical Company Limited (Takeda) and its wholly-owned subsidiary,
Takeda Pharmaceuticals U.S.A., Inc. announced that the United States (U.S.)
Food and Drug Administration (FDA) has approved NESINA (alogliptin) and the
fixed-dose combination (FDC) therapies OSENI (alogliptin and pioglitazone) and
KAZANO (alogliptin and metformin HCl) for the treatment of type 2 diabetes in
adults as adjuncts to diet and exercise.

"Takeda is pleased with the FDA approval of NESINA, OSENI and KAZANO for the
treatment of type 2 diabetes, a therapeutic category in which we have more
than twenty years of clinical and patient experience," said Douglas Cole,
president, Takeda Pharmaceuticals U.S.A., Inc. "Millions of people are
affected by diabetes and, as a leader in the diabetes arena, Takeda is
dedicated to working to advance patient care and helping to meet the needs of
this growing patient population."

NESINA is a dipeptidyl peptidase-4 inhibitor (DPP-4i) that is designed to slow
the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP
(glucose-dependent insulinotropic peptide). OSENI, which combines alogliptin
with pioglitazone, is the first product in the U.S. to include both a DPP-4i
and a thiazolidinedione (TZD) in a single tablet. KAZANO combines alogliptin
with metformin HCl, a widely used anti-diabetes medication, in a single
tablet.

The most common adverse events (greater than or equal to 4%) reported with
NESINA include nasopharyngitis, headache and upper respiratory tract
infection. With regard to OSENI, common adverse events (greater than or equal
to 4%) reported include nasopharyngitis, back pain and upper respiratory tract
infection. Common adverse events (greater than or equal to 4%) reported with
KAZANO include upper respiratory tract infection, nasopharyngitis, diarrhea,
hypertension, headache, back pain and urinary tract infection.

Takeda is committed to providing type 2 diabetes patients with treatment
options that help address their needs, and is planning to commercially launch
NESINA, OSENI and KAZANO in the summer of 2013.

Takeda's consolidated financial statements for the 2012 fiscal year will not
be impacted by the FDA approvals.

Clinical Trial Program U.S.-based Takeda Global Research & Development Center,
Inc. conducted worldwide placebo- and active-controlled clinical trials of
NESINA involving more than 13,000 patients. The safety and efficacy of NESINA
was studied as a once-daily monotherapy and in combination with several other
classes of anti-diabetic medications, including biguanides, TZDs, insulin and
sulfonylureas. In these studies, NESINA 25 mg, taken once daily, demonstrated
clinically meaningful and statistically significant improvements in hemoglobin
A1C compared to placebo.

Of the total number of patients included in the NESINA clinical trial program,
more than 3,000 were included in the studies used to support the FDA approval
of OSENI, and more than 4,000 were included in those to support the FDA
approval of KAZANO. Study results indicated that alogliptin co-administered
with either pioglitazone or metformin HCl produced significant improvements in
glycemic control as compared to the respective monotherapies.

About Type 2 Diabetes Type 2 diabetes is the most common form of diabetes
affecting millions of people globally. In fact, more than 23 million people in
the U.S. alone currently live with the disease. Type 2 diabetes is a
progressive and chronic condition and patients should work with a health care
professional to manage and monitor their disease. In addition to diet and
exercise, patients often need to take multiple medications in order to help
them manage their blood glucose levels. According to the International
Diabetes Federation, the global health care expenditures for diabetes (both
type 1 and 2) were estimated at $471.6 billion in 2012. By 2030, this number
is projected to exceed $595 billion.

About NESINA, OSENI and KAZANO NESINA is a DPP-4i for the treatment of type 2
diabetes as an adjunct to diet and exercise. DPP-4is slow the inactivation of
incretin hormones GLP-1 and GIP. As a result, an increased amount of active
incretins enables the pancreas to secrete insulin in a glucose-dependent
manner, thereby assisting in the management of blood glucose levels. A New
Drug Application (NDA) for NESINA was approved in April 2010 by the Japanese
Ministry of Health, Labour and Welfare for the treatment of type 2 diabetes,
and the therapy is available under the same brand name in Japan.

OSENI is an FDC therapy which combines alogliptin and pioglitazone in a single
tablet, for the treatment of type 2 diabetes in adults as an adjunct to diet
and exercise. Pioglitazone is a TZD that decreases insulin resistance, a
condition in which the body does not efficiently use the insulin it produces
to control blood glucose levels, and is approved in adults for the treatment
of type 2 diabetes as an adjunct to diet and exercise. An NDA for alogliptin
and pioglitazone was approved in July 2011 by the Japanese Ministry of Health,
Labour and Welfare for the treatment of type 2 diabetes, and the therapy is
currently available under the brand name LIOVEL in Japan.

KAZANO is an FDC therapy for the treatment of type 2 diabetes, which combines
alogliptin and metformin HCl in a single tablet. Metformin HCl is a biguanide,
a widely used anti-diabetes medication that acts primarily by reducing the
amount of glucose produced by the liver.

Indications

Indications for NESINA (alogliptin) 6.25 mg, 12.5 mg, and 25 mg Tablets;
KAZANO (alogliptin and metformin HCl) 12.5 mg/500 mg and 12.5 mg/1000 mg
Tablets; and OSENI (alogliptin and pioglitazone) 25 mg/15 mg, 25 mg/30 mg, 25
mg/45 mg, 12.5 mg/15 mg, 12.5 mg/30 mg, and 12.5 mg/45 mg Tablets

NESINA, KAZANO, and OSENI are indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes mellitus.

NESINA, KAZANO, and OSENI are not for treatment of type 1 diabetes or diabetic
ketoacidosis.

Important Safety Information

WARNING: CONGESTIVE HEART FAILURE—for OSENI Thiazolidinediones, including
pioglitazone, which is a component of OSENI, cause or exacerbate congestive
heart failure in some patients. After initiation of OSENI, and after dose
increases, monitor patients carefully for signs and symptoms of heart failure
(e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure
develops, it should be managed according to current standards of care and
discontinuation or dose reduction of pioglitazone in OSENI must be considered.
OSENI is not recommended in patients with symptomatic heart failure.
Initiation of OSENI in patients with established New York Heart Association
(NYHA) Class III or IV heart failure is contraindicated.

WARNING: LACTIC ACIDOSIS —for KAZANO Lactic acidosis is a rare, but serious
complication that can occur due to metformin accumulation. The risk increases
with conditions such as sepsis, dehydration, excess alcohol intake, hepatic
impairment, renal impairment, and acute congestive heart failure. The onset is
often subtle, accompanied only by nonspecific symptoms such as malaise,
myalgias, respiratory distress, increasing somnolence, and nonspecific
abdominal distress. Laboratory abnormalities include low pH, increased anion
gap, and elevated blood lactate. If acidosis is suspected, KAZANO should be
discontinued and the patient hospitalized immediately.

NESINA, KAZANO, and OSENI are contraindicated in patients with a history of
serious hypersensitivity reaction to any of the components of these products,
such as anaphylaxis, angioedema, or severe cutaneous adverse reactions. KAZANO
is contraindicated in patients with renal impairment (e.g., serum creatinine
levels greater than or equal to 1.5 mg/dL for men, greater than or equal to
1.4 mg/dL for women or abnormal creatinine clearance), which may also result
from conditions such as cardiovascular collapse (shock), acute myocardial
infarctions, and septicemia. KAZANO is contraindicated in patients with acute
or chronic metabolic acidosis, including diabetic ketoacidosis. Do not
initiate OSENI in patients with established NYHA Class III or IV heart
failure.

Warnings and Precautions—for KAZANO

Lactic acidosis: Warn against excessive alcohol intake. KAZANO is not
recommended in hepatic impairment and is contraindicated in renal impairment.
Ensure normal renal function before initiating and at least annually
thereafter. Temporarily discontinue in patients undergoing radiologic studies
with intravascular iodinated contrast materials or any surgical procedures
necessitating restricted intake of food and fluids. Lactic acidosis due to
metformin accumulation during therapy is fatal in approximately 50% of cases.
The risk increases in patients with renal impairment, congestive heart failure
requiring drug treatment, and with increasing age.

Vitamin B12 deficiency: Metformin may lower Vitamin B12 levels. Monitor
hematologic parameters annually.

Warnings and Precautions—for OSENI

Congestive heart failure: Fluid retention may occur and can exacerbate or lead
to congestive heart failure. Combination use with insulin and use in
congestive heart failure NYHA Class I and II may increase risk. Monitor
patients for signs and symptoms.

Edema: Dose-related edema may occur. Use with caution in patients with edema.

Fractures: Increased incidence in female patients. Apply current standards of
care for assessing and maintaining bone health.

Bladder cancer: Data suggest an increased risk of bladder cancer in
pioglitazone users. Data also suggest that the risk increases with duration of
use. Do not use OSENI in patients with active bladder cancer. Use caution when
using in patients with a prior history of bladder cancer. Tell patients to
promptly report any sign of hematuria or other symptoms such as dysuria or
urinary urgency as these may be due to bladder cancer.

Macular edema: Macular edema has been reported in some patients taking
pioglitazone. Recommend regular eye exams. Instruct patients to report any
visual changes promptly.

Ovulation: Therapy with pioglitazone may result in ovulation in some
premenopausal anovulatory women.

Warnings and Precautions—for NESINA, KAZANO, and OSENI

Acute pancreatitis: There have been postmarketing reports of acute
pancreatitis. If pancreatitis is suspected, promptly discontinue NESINA,
KAZANO, or OSENI.

Hypersensitivity: There have been postmarketing reports of serious
hypersensitivity reactions in patients treated with alogliptin such as
anaphylaxis, angioedema or severe cutaneous adverse reactions. In such cases,
promptly discontinue NESINA, KAZANO, or OSENI, assess for other potential
causes, institute appropriate monitoring and treatment, and initiate
alternative treatment for diabetes. Use caution in a patient with a history of
angioedema with another DPP-4i because it is unknown whether such patients
will be predisposed to angioedema.

Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal.
Causality cannot be excluded. Baseline liver test panel is recommended. If
liver injury is detected, promptly interrupt NESINA, KAZANO, or OSENI and
assess patient for probable cause, then treat cause if possible, to resolution
or stabilization. Do not restart NESINA, KAZANO, or OSENI if liver injury is
confirmed and no alternate etiology can be found. Use with caution in patients
with liver disease.

Hypoglycemia: Insulin and insulin secretagogues are known to cause
hypoglycemia. A lower dose of the insulin or insulin secretagogue may be
required to minimize the risk when used in combination with NESINA, KAZANO, or
OSENI.

Macrovascular outcomes: There have been no clinical studies establishing
conclusive evidence of macrovascular risk reduction with NESINA, KAZANO,
OSENI, or any other anti-diabetic drug.

Adverse Reactions

Most common adverse reactions (greater than or equal to 4% of patients treated
with NESINA 25 mg and more frequently than in patients who received placebo)
were nasopharyngitis (4.4%), headache (4.2%), and upper respiratory tract
infection (4.2%).

Most common adverse reactions (greater than or equal to 4% of patients treated
with co-administration of alogliptin and metformin) were upper respiratory
tract infection (8%), nasopharyngitis (6.8%), diarrhea (5.5%), hypertension
(5.5%), headache (5.3%), back pain (4.3%), and urinary tract infection (4.2%).

Most common adverse reactions (greater than or equal to 4% of patients treated
with co-administration of alogliptin and pioglitazone) were nasopharyngitis
(4.9%), back pain (4.2%), and upper respiratory tract infection (4.1%).

Drug Interactions

Use of OSENI with CYP2C8 strong inhibitors (e.g., gemfibrozil) will, or
inducers (e.g., rifampin) may, require dose adjustment.

Cationic drugs eliminated by renal tubular secretion should be used with
caution if taken with KAZANO.

Please see accompanying Full Prescribing Information , including Medication
Guide, for NESINA.

Please see accompanying Full Prescribing Information , including Medication
Guide, for KAZANO.

Please see accompanying Full Prescribing Information , including Medication
Guide, for OSENI.

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 treatments and seek to
bring innovative products to patients through a pipeline that includes
compounds in development for metabolic and cardiovascular disease,
gastroenterology, neurology and other conditions. To learn more about these
Takeda companies, visit www.takeda.us . 

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 .

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Contacts:

Elissa J. JohnsenTakeda Pharmaceuticals U.S.A., Inc.+1-224-554-3185
elissa.johnsen@takeda.com 

Corporate Communications DepartmentTakeda Pharmaceutical Company
Limited+81-3-3278-2037

Website: http://www.takeda.com
 
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