EU marketing authorization granted for three new type 2 diabetes therapies, Vipidia, Vipdomet and Incresync

Date: Sep-25-2013Takeda 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."

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.

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]

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.