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)

Fri Jan 25, 2013 6:55pm EST

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DEERFIELD, Ill.  and  OSAKA, Japan,  Jan. 25, 2013  /PRNewswire/ -- Takeda
Pharmaceutical Company Limited (Takeda) and its wholly-owned subsidiary, Takeda
Pharmaceuticals  U.S.A., Inc. today 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.  

This press release contains forward-looking statements. Forward-looking
statements include statements regarding Takeda's plans, outlook, strategies,
results for the future, and other statements that are not descriptions of
historical facts. Forward-looking statements may be identified by the use of
forward-looking words such as "may," "believe," "will," "expect," "project,"
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Forward-looking statements involve risks and uncertainties that could cause
actual results or experience to differ materially from that expressed or implied
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Takeda's business, including general economic conditions in  Japan,  the United
States  and worldwide; (2) competitive pressures and developments; (3)
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development programs; (5) actions of regulatory authorities and the timing
thereof; (6) changes in exchange rates; (7) claims or concerns regarding the
safety or efficacy of marketed products or product candidates in development;
and (8) integration activities with acquired companies.

The forward-looking statements contained in this press release speak only as of
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Contacts:

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

Corporate  Communications  Department
Takeda Pharmaceutical Company Limited
+81-3-3278-2037

SOURCE  Takeda Pharmaceutical Company Limited

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