Takeda Receives Simultaneous European Marketing Authorization for Three New Type 2 Diabetes Therapies, Vipidia[TM] ? (alogliptin) and Fixed-Dose Combinations Vipdomet[TM] ? (alogliptin and metformin)

Osaka, Japan (ots/PRNewswire) -

Takeda Pharmaceutical Company Limited (Takeda) today announced
that the European Commission has granted Marketing Authorization (MA)
for Vipidia[TM] (alogliptin), a dipeptidyl peptidase IV (DPP-4)
inhibitor, for the treatment of type 2 diabetes patients who are
uncontrolled on existing therapies[1]-[3]and for the fixed-dose
combination (FDC) therapies Vipdomet[TM] (alogliptin with metformin)
and Incresync[TM] (alogliptin with pioglitazone). The Committee for
Medicinal Products for Human Use (CHMP), of the European Medicines
Agency (EMA), issued a positive opinion for these products on July
26, 2013.

This announcement, comes shortly after publication of final
results from the cardiovascular (CV) safety outcomes trial EXAMINE[*]
in The New England Journal of Medicine (NEJM).[1] Alogliptin is the
first agent for the treatment of type 2 diabetes to be licensed with
demonstrated CV safety outcomes data[4]

"The incidence of type 2 diabetes in Europe is on the rise with an
estimated 55 million cases in 2011 predicted to increase to an
estimated 64.2 million in 2030" said Trevor Smith, Head of Commercial
Operations, Europe & Canada, Takeda. "We know that many people living
with type 2 diabetes struggle to manage their disease so there is a
need for new therapies to assist them in doing so. This Marketing
Authorization marks an important milestone in Takeda's ongoing
commitment in working to advance patient care and helping to meet the
individual needs of this growing patient population."

The MA was based on data from a robust clinical trial program
involving more than 11,000 patients treated for up to four years and
two key studies the ENDURE[*] trial and interim data from the
cardiovascular safety outcomes trial EXAMINE.

Results from the ENDURE study demonstrated that alogliptin 25 mg
in addition to metformin offered superior durability of glycemic
control at two years with notably fewer hypoglycemic episodes and no
negative impact on weight compared to a sulphonylurea (SU),
(glipizide).[5] Results also showed that when alogliptin was given in
combination with metformin, significantly more patients achieve
target HbA1c of less than or equal to 7% compared with an SU in
combination with metformin.[5]

The efficacy of alogliptin was also studied as an adjunct to diet
and exercise as an add-on therapy to several other classes of
anti-diabetic medications, including metformin, thiazolidinediones
(TZDs), insulin and SUs. In these studies alogliptin 25 mg tablets
taken once daily, demonstrated clinically and statistically
significant reductions in HbA1c, with a good overall tolerability
profile and low incidence of hypoglycemia compared with active
control or placebo.[1],[6]-[10] Previous trials indicated that
alogliptin co-administered with either metformin or pioglitazone
produced significant improvements in glycemic control compared with
the respective monotherapies.[11]-[13]

Common adverse events reported with alogliptin include upper
respiratory tract infection, nasopharyngitis, headache, abdominal
pain, gastroeosophageal reflux (GERD), pruritus and rash.[1] In
patients treated with alogliptin co-administered with metformin,
common adverse events include upper respiratory tract infection,
nasopharyngitis, headache, abdominal pain, GERD, diarrhea, vomiting,
gastritis, gastroenteritis, pruritus and rash.[2] Common adverse
events reported with patients treated with alogliptin co-administered
with pioglitazone include upper respiratory tract infection,
sinusitis, nausea, dyspepsia, abdominal pain, pruritus, peripheral
edema and increased weight.[3]

"Although there are a number of treatment options already
available, many patients still fail to meet glycemic targets,
experience hypoglycemic episodes, are overweight and remain at risk
from long-term complications, such as cardiovascular disease and
renal impairment," commented Professor Simon Heller, Professor of
Clinical Diabetes at the University of Sheffield, Sheffield, UK and
EXAMINE trial investigator. "Today's announcement, along with the
cardiovascular outcomes data from EXAMINE, means that physicians
within the European Union will have access to a comprehensive range
of new treatments to help eligible patients manage their disease.
Flexible treatments that are convenient for patients and that can
help to control the numerous and complex factors associated with type
2 diabetes, may be of value in helping to implement a more
personalized approach to care."

--------------------------------------------------

*. EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard
of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary
Syndrome

*. Efficacy and Safety of Alogliptin Plus Metformin Compared to
Glipizide Plus Metformin in Subjects With Type 2 Diabetes Mellitus;

Alogliptin is available in a range of doses suitable to treat
patients with all stages of renal impairment, including end stage
renal disease (ESRD).[1]

Takeda received approval for alogliptin (Nesina) in 2010 and in
fixed-dose combination with pioglitazone (Liovel) in 2011 in Japan.
In the US, Takeda received approval for alogliptin as a monotherapy
(Nesina) and in fixed-dose combinations with metformin (Kazano) and
with pioglitazone (Oseni) in 2013. In addition, alogliptin was
approved in China in 2013.

The approval of these MAs will not require any change of the
outlook for Takeda's consolidated results for the full year of fiscal
2013 announced on July 31, 2013.

About Vipidia (alogliptin)

- Alogliptin is indicated for the treatment of type 2 diabetes in adults
aged 18 years and older to improve glycemic control in combination with other glucose
lowering medicinal products including insulin, when these, together with diet and
exercise, do not provide adequate glycemic control[1]
- The usual recommended daily dose is 25 mg once daily (OD), with dose
flexibility for all stages of renal impairment (no dose adjustment for mild renal
impairment, 12.5 mg OD for moderate renal impairment, 6.25 mg OD for severe renal
impairment or ESRD)[1]
- DPP-4 inhibitors address insulin deficiency by slowing the inactivation of
incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent
insulinotropic peptide).[14] 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[14]

Alogliptin is currently available in Japan and the US under the
brand name Nesina.

About Vipdomet (alogliptin and metformin) fixed dose
combination[2]

Alogliptin and metformin is a FDC therapy for the treatment of
type 2 diabetes, which combines 12.5 mg alogliptin and 1000 mg
metformin in a single tablet, taken twice daily. Vipdomet is
indicated in the treatment of adult patients aged 18 years and older
with type 2 diabetes mellitus:

- as an adjunct to diet and exercise to improve glycemic control in adult
patients, inadequately controlled on their maximal tolerated dose of metformin alone,
or those already being treated with the combination of alogliptin and metformin
- in combination with pioglitazone (i.e. triple combination therapy) as an
adjunct to diet and exercise in adult patients inadequately controlled on their
maximal tolerated dose of metformin and pioglitazone
- in combination with insulin (i.e. triple combination therapy) as an adjunct to
diet and exercise to improve glycemic control in patients when insulin at a stable
dose and metformin alone do not provide adequate glycemic control

The alogliptin and metformin fixed-dose combination is currently
available in the US under the brand name Kazano.

About Incresync (alogliptin and pioglitazone) fixed dose
combination[3]

Alogliptin and pioglitazone is a FDC therapy for the treatment of
type 2 diabetes, which combines 25 mg alogliptin and 45 mg
pioglitazone in a single tablet, taken once daily. Incresync is
indicated as a second or third line treatment in adult patients aged
18 years and older with type 2 diabetes mellitus:

- as an adjunct to diet and exercise to improve glycemic control in adult
patients (particularly overweight patients) inadequately controlled on pioglitazone
alone, and for whom metformin is inappropriate due to contraindications or intolerance
- in combination with metformin (i.e. triple combination therapy) as an adjunct
to diet and exercise to improve glycemic control in adult patients (particularly
overweight patients) inadequately controlled on their maximal tolerated dose of
metformin and pioglitazone

The alogliptin and pioglitazone fixed-dose combination is
currently available in Japan under the brand name Liovel and in the
US as Oseni.

About type 2 diabetes

- In 2012, 371 million people were living with type 2 diabetes worldwide.
That number continues to grow and by 2030 it is estimated to rise to 552 million[15]
- In 2011, the number of people with diabetes in Europe was estimated to be 55
million[15]
- The number of type 2 diabetes patients is increasing in every country[15]
- In 2011, one in 10 deaths in adults in the Europe are attributed to diabetes,
representing close to 600,000 people[15]
- Estimates indicate that more than EUR 99 billion* was spent on healthcare due
to diabetes in the European region in 2011, accounting for almost one-third of global
healthcare expenditures due to diabetes[15]
- Because of the chronic nature of this disease, combination therapy is almost
uniformly required to maintain diabetic control over many years of therapy[16]

*Based on conversion of USD 131 billion,[15] where 1 EUR = 1.32942
USD as at 12 August 2013

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 people
worldwide through leading innovation in medicine. Additional
information about Takeda is available through its corporate website,
http://www.takeda.com.

References

1) Summary of product characteristics for Vipidia. Takeda Pharmaceuticals
GmBH.
2) Summary of product characteristics for Vipdomet. Takeda Pharmaceuticals GmBH.
3) Summary of product characteristics for Incresync. Takeda Pharmaceuticals
GmBH.
4) White, W.B. et al. (2013) Alogliptin after Acute Coronary Syndrome in
Patients with Type 2 Diabetes. The New England Journal of Medicine. [online] nejm.org.
Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1305889
5) Del Prato S, Camisasca R et al. Durability of the Efficacy and safety of
Alogliptin Compared to Glipizide over 2 Years When Used in Combination with Metformin.
Poster #66-LB presented at the 73rd Scientific Sessions of the American Diabetes
Association (ADA), Chicago, Illinois, June 21-25, 2013.
6) DeFronzo RA, Fleck PR, Wilson CA, et al. Efficacy and safety of dipeptidyl
peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate
glycemic control. Diabetes Care 2008;31(12):2315-2317.
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dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type
2 diabetes and inadequately controlled with metformin monotherapy: a multicentre,
randomised, double blind, placebo-controlled study. Int J Clin Pract 2009;63(1):46-55.
8) Pratley RE, Reusch JE-B, Fleck PR, et al. Efficacy and safety of the
dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with
type 2 diabetes: a randomised, double blind, placebo-controlled study. Curr Med Res
Opin 2009;25(10):2361-2371.
9) Rosenstock J, Rendell MS, Gross JL, et al. Alogliptin added to insulin
therapy in patients with type 2 diabetes reduces HbA1c without causing weight gain or
increased hypoglycaemia. Diabetes Obes Metab 2009;11:1145-1152.
10) Pratley RE, Kipnes MS, Fleck PR, et al. Efficacy and safety of dipeptidyl
peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately
controlled by glyburide monotherapy. Diabetes, Obesity and Metabolism 2009;11:167-176.
11) Pratley RE, Wilson CA and Fleck PR. Alogliptin plus metformin combination
therapy vs alogliptin or metformin monotherapy for type 2 diabetes mellitus. Presented
at the 48th Annual Meeting of the European Association for the Study of Diabetes,
Berlin 2012. Poster 841-P.
12) DeFronzo RA, Burant CF, Fleck PR, et al. Efficacy and tolerability of the
DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin treated patients
with type 2 diabetes. J Clin Endocrinol Metab 2012; 97(5):1615-1622.
13) Bosi E, Ellis GC, Wilson CA, et al. Alogliptin as a third oral antidiabetic
drug in patients with type 2 diabetes and inadequate glycaemic control on metformin
and pioglitazone: a 52 week, randomized, double-blind, active-controlled,
parallel-group study. Diabetes, Obes and Metab 2011;13(12): 1088-1096.
14) Christopher R and Karim A. Clinical pharmacology of alogliptin, a dipeptidyl
peptidase-4 inhibitor, for the treatment of type 2 diabetes. Expert Rev Clin Parmacol
2009;2(6):589-600.
15) International Diabetes Federation. IDF Diabetes Atlas, 5th edition.
Brussels, Belgium. Last accessed August 2013, available at:
http://www.idf.org/diabetesatlas.
16) Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in
type 2 diabetes: a patient centred approach. Position statement of the American
Diabetes Association and the European Association for the Study of Diabetes. Diabetes
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Date of preparation: September 2013

EUCAN/ALO/2013-10090

UK/VIP/1309/0052

ots Originaltext: Takeda Pharmaceutical Company Limited
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Contacts: Investor relations and media enquiries: Takeda
Pharmaceuticals Company Limited, Corporate Communications Department,
Telephone: +81-3-3278-2037; Takeda Pharmaceuticals International,
Inc.,
Elissa J. Johnsen, Telephone: +1-224-554-3185,
Email:elissa.johnsen@takeda.com