OSAKA Study Results met Primary Endpoint and Show That Both ADVAGRAF(R) and PROGRAF(TM) Give Similar Results in Renal Transplantation

By Astellas Pharma Europe Ltd., PRNE
Sunday, May 1, 2011

First Presentation of the Optimizing ImmunoSuppression After Kidney Transplantation with ADVAGRAF (OSAKA) Study Results at American Transplant Congress

STAINES, England, May 3, 2011 - Astellas Pharma Europe Ltd today announced that the results of the
6-month OSAKA study demonstrate that tacrolimus prolonged release (QD;
ADVAGRAF(R), Graceptor(R) in Japan)-based therapy is non-inferior to the same
daily dose of tacrolimus immediate release (BID; PROGRAF(TM))-based therapy
(0.2mg/kg/day) for efficacy in renal transplantation. These data were
presented for the first time this week at the 2011 American Transplant
Congress in Philadelphia.

In an era when there are few promising new immunosuppressants in the
pipeline for kidney transplantation, the OSAKA study investigated how to
optimise exposure to tacrolimus QD in comparison with the current clinical
standard, tacrolimus BID.

The study was conducted in 110 centres across 22 countries, and included
more than 1,200 patients. Patients and donors reflected the real-life
clinical situation, with recognised declining organ quality and an ageing
patient population. Approximately two-thirds of patients in the study were
male and mean age was around 50 years. The mean age of organ donors in the
study was 51.5 years and approximately 50% were defined as extended criteria

At 6 months, efficacy comparison revealed no significant difference
between treatment arms in the primary composite endpoint of efficacy failure.
Graft dysfunction (measured at the study end) was the primary cause of
efficacy failure in all treatment arms. The level of estimated glomerular
filtration rate (eGFR) set for graft dysfunction (<40mL/min/1.73m2) and the
high number of extended criteria donors are likely to account for the high
incidence of graft dysfunction as a reason for efficacy failure.

Incidence of biopsy-confirmed acute rejection (BCAR), time to first
incidence of BCAR and severity of BCAR were low, and comparable across
treatment arms. Renal function was similar on tacrolimus prolonged release-
and immediate release-based therapies. Interestingly, the study also showed
that a higher starting dose of tacrolimus QD (0.3mg/kg/day) is not associated
with increased efficacy. Steroid-free therapy was associated with less
reported diabetes mellitus and decreased cholesterol compared to the other
treatment arms, but lower renal function, and there were no significant
differences in adverse events between arms.

Dr Laetitia Albano from the Centre Hospitalier Universitaire de Nice,
, who presented the study results at the American Transplant Congress,
commented: 'The OSAKA study complements the previous findings of a recent
double-blind, double-dummy comparison of tacrolimus QD and BID, and
demonstrates the similarity in use of tacrolimus QD and BID in an open-label
setting which more closely represents clinical practice.'


About the OSAKA study

The OSAKA study was an international, multicentre, randomised, 24-week,
open-label, four-armed, parallel-group, comparative phase IIIb study designed
to investigate immunosuppressive regimens with tacrolimus QD or tacrolimus
BID in adult kidney transplant recipients.

Subjects (1,251) were randomised 1:1:1:1 to four treatment arms:

- Arm 1: tacrolimus BID 0.2mg/kg initial dose + mycophenolate mofetil
(MMF) + corticosteroids (24 weeks)

- Arm 2: tacrolimus QD 0.2mg/kg initial dose + MMF + corticosteroids (24

- Arm 3: tacrolimus QD 0.3mg/kg initial dose + MMF + corticosteroids (24

- Arm 4: tacrolimus QD 0.2mg/kg initial dose + MMF + basiliximab +
perioperative corticosteroids (bolus)

The primary composite endpoint was efficacy failure rate, defined as the
incidence of and time to first incidence of graft loss, BCAR or graft
dysfunction (defined as eGFR <40mL/min/1.73m2 at Week 24). This endpoint was
used in accordance with the European Medicines Agency guideline on clinical
investigation of immunosuppressants for solid organ transplantation.(1)
Secondary endpoints included renal function, assessment of acute rejections
(incidence, time, severity and overall frequency), and graft and patient

About tacrolimus

Tacrolimus has become an established immunosuppressive agent for the
prophylaxis and treatment of renal allograft rejection. It is available
worldwide as a twice-a-day formulation (PROGRAF) and as a prolonged-release
formulation (ADVAGRAF), which has been developed to provide once-daily
dosing. The prolonged-release formulation allows tacrolimus to be available
for absorption over a greater proportion of the gastrointestinal tract, which
may reduce day-to-day variability in bioavailability and deliver more
consistent long-term tacrolimus blood levels.(2)

About Astellas Pharma Europe Ltd

Astellas Pharma Europe Ltd, located in the UK, is the European
Headquarters of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical
company dedicated to improving the health of people around the world through
the provision of innovative and reliable pharmaceuticals. The organisation is
committed to becoming a global company by combining outstanding research and
development (R&D) and marketing capabilities and continuing to grow in the
world pharmaceutical market. Astellas Pharma Europe Ltd manages 21 affiliate
offices located across Europe, the Middle East and Africa. In addition, the
company has an R&D site and three manufacturing plants in Europe. The company
employs approximately 3,900 staff across these regions. For more information
about Astellas Pharma Europe, please visit

About the American Transplant Congress

The 2011 American Transplant Congress is the 11th joint annual meeting of
the American Society of Transplant Surgeons and the American Society of
Transplantation. The meeting was held from 30 April to 4 May 2011 at the
Pennsylvania Convention Center in Philadelphia.

The congress programme aims to provide a forum for exchange of new
scientific and clinical information, create an arena for the interchange of
ideas regarding care and management issues, and facilitate discussions of the
socioeconomic, ethical and regulatory issues related to solid organ and
tissue transplantation.


1. European Medicines Agency Committee for Medicinal Products for Human
Use. Guideline on clinical investigation of immunosuppressants for solid
organ transplantation. London, 24 July 2008.

2. European Medicines Agency Committee for Proprietary Medicinal
Products. Note for guidance on modified release oral and transdermal dosage
forms: section II (pharmacokinetic and clinical evaluation). London, 28 July

Contact for enquiries or additional information: Mindy Dooa, Director, Corporate Communications, Astellas Pharma Europe Ltd, +44(0)1784-419-408, mindy.dooa at

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