Professional Documents
Culture Documents
August 2008
Technology description
Everolimus (RAD-001; Certican), a proliferation signal inhibitor (of the mammalian
target of rapamycin [mTOR] protein), is an oral immunosuppressant that targets the
primary causes of progressive allograft dysfunction (also known as chronic rejection)
following organ transplantation. It is anticipated that everolimus will be used in
combination with ciclosporin and corticosteroids, and as a substitute for sirolimus,
azathioprine or mycophenolic acid. Everolimus is administered at 1.5-3.0mg daily, with
dose adjustment to achieve defined trough blood levels.
Everolimus is in phase III clinical trials within a drug-eluting stent for coronary artery
restenosis, as prophylaxis of liver transplant rejection, and for renal cancer and
neuroendocrine tumours.
Developer
Novartis Pharmaceuticals UK Ltd.
Relevant guidance
Renal transplantation:
NICE technology appraisal. The clinical effectiveness and cost effectiveness of
immuno-suppressive therapy for renal transplantation in adults. 2004 1 .
NICE clinical guideline in development. Kidney disease: Early identification and
management of adults with chronic kidney disease in primary and secondary care.
Expected September 2008 2 .
UK Renal Association. Clinical Practice Guidelines: assessment for renal
transplantation. 2008 3 .
Cardiac transplantation:
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NICE clinical guideline. Chronic heart failure management of chronic heart failure
in adults in primary and secondary care. Issued July 2003. Guideline warrants a partial
update after March 2008 review 4 .
SIGN. Chronic heart failure. 2007 5 .
In 2001, there were around 13,900 patients receiving immunosuppression after kidney
transplantation in England and Wales. In 2001, about 1,500 new renal transplants were
performed in England and Wales, with about 21% of organs coming from live donors.
Over 90% of these transplants were performed in people aged 18 years. The median age
of all adults receiving a kidney transplant in 2001 was 49 years. There is a 710% annual
increase in the UK dialysis population, and the number of people needing a transplant is
expected to rise over the next decade1.
There were 162 heart transplants in the UK between 1st April 2006 and 31st March 2007 8 .
Although there are no randomised studies of transplantation in patients with heart failure
owing to the intrinsic practical limitations in this field, observational data demonstrate an
improved quality of life after transplantation, with a 7080% survival at five years. Long-
term prognosis is limited by the side effects of immunosuppression, such as hypertension,
malignancy, renal failure and infection, and the development of graft vascular disease3.
Trial code CRAD001A253: de novo heart transplant; everolimus vs azathioprine; phase III 14,15 .
Status Published
Design Randomised, double blind, controlled.
Participants n=634; adults; de novo heart transplant.
in trial Randomised to everolimus 1.5mg or 3.0 mg or azathioprine. All in combination with
ciclosporin, corticosteroids and statins.
Follow-up 6, 12, 24 months and open label extension through 48 months
Primary Composite of death, graft loss or re-transplantation, loss to follow-up, biopsy-proved
4
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5
August 2008 National Horizon Scanning Centre
News on emerging technologies in healthcare
Patients
; Reduced morbidity Reduced mortality or increased ; Improved quality of life for
survival patients and/or carers
Quicker, earlier or more accurate Other: None identified
diagnosis or identification of
disease
Services
Increased use Service reorganisation required Staff or training required
Costs
Increased unit cost compared to Increased costs: more patients Increased costs: capital
alternative coming for treatment investment needed
New costs: Savings: ; Other: unsure of relative cost.
References
1
National Institute of Health and Clinical Excellence. The clinical effectiveness and cost effectiveness of
immuno-suppressive therapy for renal transplantation. NICE technology appraisal TA85. September 2004.
2
National Institute of Health and Clinical Excellence. Kidney disease: Early identification and management of
adults with chronic kidney disease in primary and secondary care. NICE clinical guideline in development.
Expected September 2008 (12th wave).
3
UK Renal Association. Clinical Practice Guidelines: assessment for renal transplantation. March 2008.
Available at: http://www.renal.org/guidelines/print/transplantationguidelinesFINALApril08.pdf (accessed
11.8.08).
4
National Institute of Health and Clinical Excellence. Chronic heart failure management of chronic heart
failure in adults in primary and secondary care. Clinical Guideline CG5. 2003 (review date February 2008)
5
Scottish Intercollegiate Guidelines Network (SIGN). Chronic heart failure. 2007. Available at:
www.sign.ac.uk/pdf/pat95.pdf (accessed 13.8.08).
a
British National Formulary. No. 55 March 2008. For an average 67.5kg adult.
6
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News on emerging technologies in healthcare
6
Webster AC, Lee VW, Chapman JR et al. Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for
primary immunosuppression in kidney transplant recipients. Available at: http://www.cochrane.org
/reviews/en/ab004290.html (accessed 13.8.08).
7
Woodroffe R, Yao GL, Meads C. Clinical and cost effectiveness of newer immunosuppressive regimens in
renal transplantation: a systematic review and modelling study. Health Technology Assessment 2005; 9: 21.
Available at: http://www.ncchta.org/execsumm/summ921.shtml (accessed 11.8.08).
8
UK Transplant Organisation. Transplant activity in the UK. Available at: https://www.uktransplant
.org.uk/ukt/statistics/transplant_activity_report/current_activity_reports/ukt/transplant_activity_uk_2006-
2007.pdf. (accessed 12.8.08).
9
Taylor AL, Watson CJ, Bradley JA. Immunosuppressive agents in solid organ transplantation: mechanisms of
action and therapeutic efficacy. Critical Reviews in Oncology and Haematology. 2005;56(1):23-46.
10
Lorber MI, Mulgaonkar S, Butt KM et al. Everolimus versus mycophenolate mofetil in the prevention of
rejection in de novo renal transplant recipients: a 3-year randomised, multicenter, phase III study.
Transplantation. 2005; 80(2):244-52.
11
Vitko S, Margreiter R, Weimar W et al. Three year efficacy and safety results from a study of everolimus
versus mycophenolate mofetil in de novo renal transplant patients. American Journal of Transplantation.
2005;5(10):2521-30.
12
Clinical trials. Efficacy and safety study of everolimus plus cyclosporine and mycophenolic acid plus
cyclosporine in kidney transplants. Available at: http://clinicaltrials.gov/ct2/show/NCT00251004 (accessed
12.8.08).
13
Clinical trials. Concentration controlled everolimus with reduced dose Neoral versus mycophenolate mofetil
with standard dose Neoral in de novo renal transplant adult recipients treated with basiliximab and
corticosteroids. Available at: http://clinicaltrials.gov/ct2/show/NCT00658320?term=NCT006
58320&rank=1(accessed 12.8.08).
14
Vigano M, Tuzcu M, Benza R et al. Prevention of acute rejection and allograft vasculopathy by everolimus in
cardiac transplant recipients: a 24 month analysis. Journal of Heart and Lung Transplant. 2007; 26(6): 584-92.
15
Eisen HJ, Tuzcu M, Dorent R et al. Everolimus for the prevention of allograft rejection and vasculopathy in
cardiac transplant recipients. The New England Journal of Medicine. 2003; 349(9): 847-858.
16
Clinical trials. Efficacy and safety of everolimus in de novo heart transplant recipients. Available at:
http://clinicaltrials.gov/ct2/show/NCT00150046 (accessed 13.8.08).
17
Lehmkuhl H, Livi U, Arizon J et al. Results of a multicenter, randomised trial of everolimus with reduced
exposure cyclosporine versus MMF and standard exposure cyclosporine in de novo cardiac transplant
recipients. The Journal of Heart and Lung Transplantation. 2008; 27(2) Suppl S65.
18
Clinical trials. Efficacy and safety of everolimus in recipients of heart transplants to prevent acute and chronic
rejection. Available at: http://clinicaltrials.gov/ct2/show/NCT00300274?term= NCT00300274&rank=1
(accessed 12.8.08).
The National Institute for Health Research National Horizon Scanning Centre Research
Programme is funded by the Department of Health.
The views expressed in this publication are those of the author and not necessarily those of the
NHS, the NIHR or the Department of Health