Data from one of Europe’s largest independent liver transplant registries reveals improved graft survival benefit in patients receiving Advagraf™ prolonged release tacrolimus compared to those on tacrolimus immediate release

EMBARGOED UNTIL 00.01 20th FEBRUARY 2015
For pan-European medical and consumer media

CHERTSEY, England, Feb. 20 2015 /PRNewswire/ – Results from a large retrospective data analysis published in the American Journal of Transplantation (AJT) today, showed that liver transplantation patients who were treated early with Advagraf experienced a significantly increased graft survival benefit of 8% at 3 years post-transplant compared with patients treated with the current standard of care, tacrolimus immediate release (twice daily).ⁱ

The number of organ transplantations is increasing every year. Nearly 6,000 liver transplants are performed each year in Europe.ⁱⁱ A liver transplant is considered when the liver no longer functions adequately.ⁱⁱⁱ Current long-term survival in liver transplantation remains sub-optimal with only 54% graft survival at 10 yearsⁱⁱ and, with increasing use of older and marginal donors, maintaining these results represents a challenge.

The aim of the ELTR study was to assess the impact of early use of Advagraf versus tacrolimus immediate release (twice daily) and the classical risk factors on long-term transplanted organ survival using real-world ELTR data.ⁱ The study was a retrospective data analysis of liver transplant patients (>18 years old) receiving either Advagraf (n=528) or tacrolimus immediate release (n=3,839) within the first month of transplantation and with a follow-up period of up to three years.ⁱ Data was collated over a five year period (Jan 2008 – Dec 2012) from 21 centres that were using both formulations in patients surviving the first month post-transplant.ⁱ

As with any registry based study, there are a number of limitations that must be considered when interpreting these data. Recognising this issue the ELTR carried out additional analysis and when patients were propensity score matched for baseline characteristics, the significant long-term graft survival advantage with Advagraf was confirmed.ⁱ

Advagraf and tacrolimus immediate release (twice daily) are immunosuppressants that are licensed for the prevention of organ rejection in patients receiving liver and kidney transplants.^iv Advagraf is a prolonged release formulation, which is an advancement on immediate release whereby the active substance delivers a more consistent exposure. This means that the treatment can also be taken once a day, rather than twice a day as with tacrolimus immediate release.ⁱⁱⁱ

Prof René Adam, Head of the Oncological Surgery and Transplant Unit of the Hepato Biliary Centre, Paul Brousse Hospital, Villejuif, France said: “Liver transplantation offers patients with liver failure a second chance at life. This real world ELTR data is the largest in Europe and clearly shows that patients receiving Advagraf once daily showed improved graft survival compared with patients receiving twice-daily tacrolimus. We hypothesize that differences between the treatment regimens, including improved adherence to treatment and reduced variability of tacrolimus exposure observed with prolonged-release tacrolimus may have long-term beneficial effects.”

Ivan Gardini, President of Educazione, informazione e Prevenzione sull’Epatite C (EpaC), the largest Italian liver patient association and liver transplant patient said: “This data is exciting, not just because it is real-world data, but also because it shows extended graft survival compared to the current standard of care. It is promising to see such robust real-world data and represents a significant step forward in liver transplantation.”

Dr. Ayad Abdulahad, Senior Vice President Medical Affairs and Health Economics, Astellas Pharma EMEA Limited comments: “At Astellas we continually seek to improve our understanding of our products’ profiles in clinical practice by evaluating clinical data sets arising from different sources, studies and methodologies. By taking this approach, Astellas hopes to build a better understanding of its products’ effectiveness to inform the most appropriate treatment approach for each patient’s needs.”

“Astellas regards continued collaboration with the transplant community as the most valuable way to develop this insight and are proud to have supported the ELTR analysis of liver transplant recipients. Hopefully this updated perspective on tacrolimus translates into improved survival for new and existing transplant recipients.”

Dr Martin Hurst Senior Medical Director Astellas said: “Astellas is dedicated to delivering innovative and high quality treatments to transplant patients and continually strive to impact a positive effect on the future of patients’ lives. These data demonstrate that the unique formulation of Advagraf, an advancement on immediate release tacrolimus, has the potential to benefit thousands more liver transplant patients and those patients on the transplant waiting list across Europe and highlights Astellas’ commitment within the field of transplantation.”

Notes to editors

The aim of the ELTR study was to assess the effect of early use of Advagraf versus tacrolimus immediate release (twice daily) on long-term survival after liver transplantation using real-world ELTR data and the classical risk factors.ⁱ The European Liver Transplant Registry (ELTR) is one of the largest and most robust registries, representing over 98% of the overall European liver transplant data from 153 centres across 27 countries.^v

The study was a retrospective analysis of liver transplant patients (>18 years old) receiving either Advagraf (n=528) or tacrolimus immediate release (n=3,839) within the first month of transplantation from 21 active transplant centers using both formulations with a follow-up period of three years.ⁱ Data was collated over a five year period (Jan 2008 – Dec 2012) and the primary outcome measures were transplanted organ and patient survival rates.ⁱ Only those patients whose newly transplanted organ was still functioning at 1 month were included in the analysis.ⁱ

An 8% organ survival advantage was seen in the Advagraf arm versus tacrolimus immediate release, meaning the newly transplanted organs of patients treated with Advagraf were more likely to still be functioning three years post-transplant compared with those treated with tacrolimus immediate release (88% vs. 80%, p=0.01).ⁱ

As with any registry based study, there are a number of limitations that must be considered when interpreting these data. Recognizing this issue the ELTR carried out additional analysis and when patients were matched for baseline characteristics, the significant 8% long-term graft survival advantage was confirmed.ⁱ

About Advagraf

Advagraf is a prolonged release formulation, an advancement on tacrolimus immediate release, whereby the active substance delivers a more consistent exposure. This means that Advagraf can also be taken once a day, rather than twice a day as with tacrolimus immediate release.^iv

Non-adherence is commonly reported within patients who receive an organ transplant, reaching levels as high as 73% in liver transplant patients.^vi,vii Compared to tacrolimus immediate release, Advagraf has been shown to improve patient adherence to treatment^viii,ix,x,xi and has been shown to reduce high levels of variability in drug levels delivering a more consistent exposure.^ix,xii,xiii

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 [email protected], (+1) 847.682.7471.

About Astellas in Transplantation

Astellas Pharma EMEA is a major player in the transplantation community. Its products for immunosuppresion are recognised worldwide in the prevention of organ rejection following kidney and liver transplantation.

Astellas Pharma EMEA remains focused on investing in its pipeline of potential future immunosuppressant therapies and are continually striving to advance transplant care by developing both new treatment regimens and innovative therapies that target specific pathways.

The number of organ transplantations is increasing every year. Nearly 6,000 liver transplants are performed each year in Europe.ⁱⁱ Current long-term survival in liver transplantation remains sub-optimal with only 54% graft survival at 10 yearsⁱⁱ and, with increasing use of older and marginal donors, maintaining these results represents a challenge.

Astellas is committed and dedicated to having a positive effect on the future of patient’s lives. Astellas is proud to contribute to the transplant community, supporting patient organisations and sponsoring the biennial World Transplant Games.

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.

Dr Martin Hurst
Senior Medical Director
Astellas Pharma EMEA

Mark Seymour
Account Director
Reynolds-MacKenzie
Tel: +44(0)20-7861-2812

References

i. Adam R, Karam V, Delvart V, et al. Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry. Am J Transpl 2015; doi: 10.1111/ajt.13171 
ii. Adam R, Karam V, Delvart V et al. J Hepatol 2012 Sep; 57(3): 675‐88
iii. Digestive Disorders Health: Liver Transplantation. Web MD available at http://www.webmd.com/digestive-disorders/digestive-diseases-liver-transplantation; Last accessed December 2014
iv. European Medicines Agency. Advagraf Summary of Product Characteristics (SPC) available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000712/WC500022234.pdf
v. European Liver Transplant Registry Centers. Available at http://www.eltr.org/spip.php?page=centers Last accessed February 2015
vi. Stilley CS, et al. Prog Transplant 2010;20(1):58–66
vii. Burra P, et al. Liver Transpl 2011; 17:760-770
viii. Beckebaum S et al. Transpl Int 2011;24:666-675;
ix. Eberlin M et al. Transplant Proc 2013;45:2314-2320
x. Kuypers DR et al Transplantation  2013;95:333-340
xi. Valente G et al Transplant Proc 2013;45:1273-1275
xii. Kurnatowska I et al. Transplant Proc 2011;43:2954−2956
xiii. Wu MJ et al. Transplantation 2011;92:648−652