DIAMOND (ADVAGRAF Studied in Combination With Mycophenolate Mofetil (MMF) and Basiliximabin Liver Transplantation) Study Provides Insights Into Kidney Function and the Prophylaxis of Organ Rejection in Liver Transplant Patients

CHERTSEY, England, February 24, 2015 /PRNewswire/ --

Publication of Primary Results in the American Journal of Transplantation (AJT)

In liver transplant patients, late renal failure is a significant cause of morbidity and is associated with premature mortality^[1],[2],[3]

Data published last week in the American Journal of Transplantation (AJT) demonstrate that in liver transplant patients, initiating lower dose ADVAGRAF™ capsules (prolonged-release tacrolimus) therapy immediately post transplant, in combination with basiliximab, results in significantly better renal function and a lower incidence of acute organ rejection when compared with patients starting at the maximum recommended dose of ADVAGRAF therapy.^[4]

Results from the DIAMOND (ADVAGRAF studied In combinAtion with MycOphenolate mofetil (MMF) aND basiliximab in liver transplantation) study show that during the immediate post-transplant period, initial administration of ADVAGRAF in mid-range of recommended dose which is up to 25% lower than the maximum recommended dose (0.15-0.175mg/kg/day) plus basiliximab (without maintenance corticosteroids) and MMF was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and acute rejection incidence compared to prolonged-release tacrolimus administered at maximum recommended dose (0.2mg/kg/day) with the same concomitant medications. Additional findings were that delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate post-transplant administration, but acute rejection incidence was comparable.

"These data provide interesting insights into the relationship between immunosuppressive treatment in the immediate post-operative period and kidney function," comments Dr Martin Hurst, Senior Medical Director in Transplantation, Astellas Pharma EMEA.

Dr Pavel Trunečka, lead author of the publication, said "Renal function is a vital predictor of long-term transplant success; the DIAMOND study suggests potential for balancing the risk of rejection, whilst minimising the risk of renal damage and potentially reducing the risk of long-term complications. This study shows that lower dose ADVAGRAF, given immediately post-transplantation, offers the potential advantages of an immunosuppressive regimen which minimises risk of graft rejection whilst preserving renal function without the need for maintenance steroids. In turn, this offers the real possibility of simplifying immunosuppression in the early post- transplant period for most liver transplant recipients."

NOTES FOR EDITORS 

About ADVAGRAF™ and tacrolimus 

Tacrolimus is a leading immunosuppressive drug used for the prevention of transplant allograft rejection after organ transplantation. It is available worldwide as a twice-a-day formulation (PROGRAF™) and as a prolonged-release formulation (ADVAGRAF™), which provides more consistent tacrolimus exposure. Tacrolimus levels require careful management to maintain sufficient exposure of tacrolimus for the prevention of transplant allograft rejection, whilst avoiding excessive levels that may increase the risk of serious side effects. The prolonged-release formulation of ADVAGRAF allows tacrolimus to be available for absorption over a greater proportion of the gastrointestinal tract. This alteration in release profile provides the potential for reduced variability in tacrolimus exposure, achieving and maintaining consistent target trough levels with a reduced requirement for dose adjustments, and improved medication adherence as a single, morning dose.^[5],[6]

The information included within this release is intended for a European audience only and differs from the approved uses for oral tacrolimus in the United States. For further information on United States prescribing information please contact Marjorie Moeling, Director, Product Communications & Advocacy, Hospital & Transplant, Astellas on Marjorie.Moeling@astellas.com, (+1)-847-682-7471.

About DIAMOND 

DIAMOND is a multicentre, randomised study involving 901 patients designed to investigate renal function with ADVAGRAF prolonged-release capsules (tacrolimus). Patients received either prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab induction therapy; tacrolimus (initial dose: 0.2mg/kg/day) or tacrolimus (0.2mg/kg/day delayed to day 5) plus basiliximab.^[4] All patients received MMF and maintenance steroids were not used.

In the study, patients on a lower dose of tacrolimus (0.15-0.175mg/kg/day) plus MMF and induction therapy (without maintenance steroids) had a higher eGFR than those treated with tacrolimus (0.2mg/kg/day) vs tacrolimus (0.2mg/kg/day delayed to day 5) plus basiliximab (76.4 vs 67.4 vs 73.3mL/min/1.73m^[2]). Patients on the lower dose tacrolimus regimen also had a significantly better rejection free survival when compared with other regimens (85.7% vs 79.9% vs 79.6%). Adverse events were comparable between all treatment regimens.^[4]

About Astellas Pharma Europe Ltd.  

Astellas Pharma Europe Ltd. operates in 40 countries across Europe, the Middle East and Africa, and is the EMEA regional business 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's focus is to deliver outstanding R&D and marketing to continue growing in the world pharmaceutical market. Astellas' presence in Europe also includes an R&D site and three manufacturing plants. The company employs over 4,500 people across the EMEA region. In 2013 Astellas was awarded SCRIP Pharmaceutical Company of the Year in recognition of its commercial success and pipeline development.

References

1. Cohen AJ, et al. Chronic Renal Dysfunction Late After Liver Transplantation. Liver Transpl. 2002 Vol 8, No 10 (October): pp 916-921.

2. Fisher NC, et al. Chronic Renal Failure Following Liver Transplantation. Transplantation. 1998; 66:59-66.

3. Ojo AO, et al. Chronic Renal Failure after Transplantation of a Nonrenal Organ. N Engl J Med. 2003; 349:931-40.

4. Trunečka P et al. Renal function in de novo liver transplant recipients receiving different prolonged-release tacrolimus regimens - the DIAMOND study. Am J Transplant 2015; doi: 10.1111/ajt.13182

5. Abrams et al. Role of tacrolimus prolonged release in the prevention of allograft rejection. Transpl Research and Risk Management, 2010:2 65-70.

6 European Public Assessment Report (EPAR). Advagraf. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000712/WC500022235.pdf . Last accessed February 2015.