Advagraf(R) Now Approved Across Europe as a Once-Daily Immunosuppressant in Organ Transplantation

London (ots/PRNewswire) - Astellas announced today that the
European Commission has approved the immunosuppressant Advagraf(R)
(generic name: tacrolimus, prolonged release) for prophylaxis of
transplant rejection in adult kidney or liver allograft recipients
and for the treatment of allograft rejection resistant to treatment
with other immunosuppressive drugs in adult patients throughout the
European Union (EU).

Advagraf(R) combines the proven safety and high efficacy of
Prograf(R), the leading immunosuppressive agent of care for the
prevention of rejection in organ transplantation, in a prolonged
release formulation that offers patients a convenient, once-daily
dosing option.

"A number of studies indicate that non-adherence to medication has
become a key concern in transplant patients and the availability of a
once-daily dosing regimen represents a highly desirable step forward
in patient management," said Professor Johannes van Hooff, Professor
of Medicine, Department of Nephrology at University Hospital
Maastricht, The Netherlands. "Advagraf(R) has the potential to
improve adherence and hence the long-term efficacy of
immunosuppression."

Transplant patients are prescribed a variety of medications that
require multiple dosing at various times throughout the day. Because
of the variety of medications and the complicated dosing schedule,
non-compliance rates for transplant recipients can be over 45 per
cent(1), resulting in acute and chronic rejection and graft loss(2).
A recent study in kidney transplant recipients was able to show a
statistically significant improvement in adherence associated with
once-daily dosing compared with twice-daily dosing regimens(3).

Clinical data overview

The EU approval of Advagraf(R) is based on the results of Phase II
trials in liver, kidney and heart transplant patients (n=613) and a
phase III trial(4) (n=638). These studies have confirmed the safety
and efficacy of once-daily Advagraf(R) to be similar to that of
twice-daily Prograf(R).

The 638 adult kidney transplant recipients in the Phase III trial
were randomised 1:1:1 and received Advagraf(R), Prograf(R) or
ciclosporin. All patients received standard basiliximab induction,
mycophenolate mofetil (MMF) and corticosteroids. The primary efficacy
endpoint was the efficacy failure rate - a composite endpoint that
included all patients who died, had graft loss (returned to dialysis
or re-transplanted), biopsy proven acute rejection (BPAR) or lost to
follow-up. A pre-specified non-inferiority margin of 10% was used to
compare efficacy failure rate.

The demographics and baseline characteristics among all groups
were similar. The one-year results showed that for efficacy failure
rate, both Advagraf(R) and Prograf(R) groups were non-inferior to
ciclosporin and had significantly less treatment failure and
crossover due to treatment failure. Overall, the side-effect profiles
of Advagraf(R) and Prograf(R) were comparable. One-year patient and
graft survival were comparable between Advagraf (98.6% and 96.7%) and
Prograf (95.7% and 92.9%).

The Advagraf(R) and Prograf(R) groups had significantly higher
creatinine clearance (Cockcroft & Gault estimates: 58.7 mL/min, 57.7
mL/min) compared to the ciclosporin group (54.6 mL/min), less use of
antibody therapy for rejection (3.7%, 2.8% compared with 8.5%) and
better lipid profiles (LDL cholesterol: 102.4 mg/dL, 97.1 mg/dL
compared with 113.4 mg/dL) than ciclosporin.

About Advagraf(R)

Advagraf(R) will be available as early as June 2007 in the UK and
Germany, followed by launches in additional European countries
throughout the year and in 2008.

About Astellas

Astellas Pharma Europe Limited, located in the UK, is a European
subsidiary 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
pharmaceutical products. The organisation is committed to becoming a
global pharmaceutical company by combining outstanding R&D and
marketing capabilities and continuing to grow in the world
pharmaceutical market. Astellas Pharma Europe is responsible for 19
affiliate offices located across Europe, the Middle East and Africa,
2 R&D establishments and 3 manufacturing plants with approximately
3,000 staff.

(1) Greenstein, S., Siegal B. Compliance and Noncompliance in
Patients with a Functioning Renal Transplant: A Multicenter Study.
Transplantation 1998; 66(12): 1718-1726.

(2) Denhaerynck, K., Dobbels, F., Cleemput, I., et al. Prevalence,
consequences and determinants of nonadherence in adult renal
transplant patients: a literature review. Transplant Int 2005;
18(10): 1121-1133.

(3) Weng, FL., Israni, AK., Joffe, MM., et al. Race and
electronically measured adherence to immunosuppressive medications
after deceased donor renal transplantation. J Am Soc Nephrol 2005;
16(6): 1839-1848.

(4) Silva, HT. Jr., Yang, HC., Aboulijoud, M., et al. for the
Tacrolimus Extended-Release De Novo Kidney Study Group. One-year
results with extended-release tacrolimus/MMF, tacrolimus/MMF and
cyclosporine/MMF in de novo kidney transplant recipients. Am J
Transplant 2007; 7(3):595-608.

ots Originaltext: Astellas Pharma Europe Limited
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Contacts: Polly Dryden, Head of Corporate Affairs, Europe, Astellas
Pharma, Tel: +44-(0)1784-419-417


	hier anmelden...