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

STAINES, England, May 3, 2011 /PRNewswire/ -- 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 donors.

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, France, 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.'

BACKGROUND

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 weeks)

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

- 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 survival.

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 http://www.astellas.eu

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.

References

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 1999.