24 July 2006, Basel, Switzerland -- The largest ever comparative transplantation study, involving 1,645 kidney transplant patients, has revealed the best immunosuppressant drug regimen that will give patients a better chance of a normal life. CellCept (mycophenolate mofetil) plus low-dose tacrolimus, corticosteroids and IL-2 induction therapy was shown to be the top combination to prevent patients rejecting their new kidney whilst maximising the function and life of the new organ.
The results at 12 months showed significantly improved kidney function (15%, p<0.0001), up to a further 65% reduction in early rejection and up to 6% improvement in organ survival for patients receiving the CellCept plus low-dose tacrolimus combination. This could mean that, if all first time kidney recipients were to take this regimen, nearly 2,500* organs could be saved in the first year post transplant.
"The results of the SYMPHONY study are an exciting and long-awaited development for both patients and doctors," commented lead investigator, Professor Henrik Ekberg, from University Hospital, Malmö, Sweden, following the study's presentation at the World Transplant Congress, Boston. "New immunosuppressant drugs have successfully reduced the rejection rates of the new organ. However, patients still face developing serious side effects from the life long use of some of these drugs. The focus is now to define the optimal balance of these combinations in order to prolong further the life of the patient and their transplanted organ. SYMPHONY now provides the answer for doctors that the best regimen for patients today is CellCept and low dose tacrolimus, steroids and induction therapy."
To prevent rejection of a new kidney by the patient's immune system, immunosuppressant combinations have traditionally contained high dose calcineurin inhibitor's (CNIs), which are now known to cause kidney damage due to toxic side effects. This damage can lead to loss of the new kidney and a return to dialysis.[i] The toxic build up of some combinations can also lead to other complications, such as diabetes and cardiovascular disease, which is the leading cause of death post transplant.[ii]
The transplant community has strongly acknowledged the need for proven strategies to reduce long term toxicity and improve long term survival. The SYMPHONY study provides the first step towards a better understanding of optimal immunosuppressive management.
Notes to editors
The purpose of the SYMPHONY study was to compare standard immunosuppression versus three regimens with low-dose or no CNI in de-novo kidney transplant patients over one year.
RESULTS
| At 12 months | N | Kidney function(GFR) | Acute rejection(BPAR) | Organ survival(Graft survival) | Patient survival median |
| (ml/min) | % | % | % | ||
| Normal dose Cyclosporine | 385 | 56.8 | 25.3 | 90.0 | 96.5 |
| Low dose Cyclosporine | 399 | 60.9 | 23.5 | 93.1 | 98.2 |
| Low dose tacrolimus | 402 | 65.4 | 12.3 | 94.2 | 97.2 |
| Low dose sirolimus | 399 | 57.3 | 35.3 | 89.2 | 96.8 |
- In this prospective, randomised, open study 1,645 patients in 15 countries were randomised to one of the four treatment regimens
- The primary objective was to determine kidney function, GFR (glomerular filtration rate), at 12 months, by measuring the amount of urine the kidney produces per minute. Secondary endpoints included biopsy proven acute rejection (BPAR), patient and graft survival
- Differences between GFR and BPAR were statistically significant among the 4 groups (p<0.0001)
- The authors concluded that IL-2 induction, standard-dose CellCept (1g bid), low-dose tacrolimus and corticosteroids provides the most optimal balance between efficacy and toxicity
Roche is strongly committed to improving the long-term outcomes of transplantation and enhancing the quality of life of transplant recipients. Roche has developed innovative therapies that improve graft and post-transplant health: CellCept is the cornerstone of low toxicity immunosuppressant therapies. CellCept, the largest selling branded immunosuppressant in North America, offers both physicians and patients the possibility of an effective long-term immunosuppressant regimen with low toxicity. Zenapax prevents the acute rejection of the newly transplanted organ. Valcyte was developed for the prevention of cytomegalovirus, a dangerous viral infection associated with transplantation. In addition, Roche supports basic research in transplantation with its funding of the independent Roche Organ Transplantation Research Foundation (ROTRF), which directly supports innovative research projects attracting new researchers with novel scientific ideas to meet unmet medical needs in solid organ transplantation.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (www.roche.com).
For further information please contact:
Julia Pipe
Roche
International Communications Manager, Transplant
Mobile tel: +41 79 263 9715
Office tel: +41 61 687 4376
Email: julia.pipe@roche.com
References
[i] Nankivell BJ et al. Calcineurin inhibitor nephrotoxicity; longitudinal assessment by protocoal histology. Transplantation 2004; 78: 557-65.
[ii] Ojo AO, Hanson JA, Wolfe RA, et al. Long-term survival in renal transplant recipients with graft function. Kidney Int. 2000;57:307-313.
*Based on figures from World Health Organisation. Human organ and tissue transplantation, report by the Secretariat. Geneva: World Health Organisation, May 2003.