darbepoitein (nesp) clinical use

1. Confidential Feb. 2016
Pharmacoeconomic
considerations in the use of
Darbepoetin alfa
Dr. Jan Melvin Zapanta

2. The “Ideal” ESA
 Effective
 Safe, Easy to use
 Flexible administration route
 Less frequent administration schedule
 Cost Effective

3. Characteristic features of NESP®
• NESP® is a long-acting erythropoiesis-stimulating agent
(ESA) that was developed as a result of application of
genetic engineering and glycoengineering after studying the
appropriate balance between receptor-binding affinity,
serum half-life, and biological activity.

4. Adapted from Egrie J.C. et al. Nephrol.Dial.Transplant. 16 (Suppl 3):3-13, 2001
Biological activity
Serum half-life
Erythropoietin receptor-binding affinity
N-linked carbohydrate chains：3
Maximum sialic acid：14
EPO Erythropoietin variant Darbepoetin alfa
： Sialic acid
： N-linked carbohydrate ： N-linked carbohydrate
N-linked carbohydrate chains：4
Maximum sialic acid：18
N-linked carbohydrate chains：5
Maximum sialic acid：22
Comparison of biological structure of
Darbepoetin alfa and EPO

5. 5
Characteristic features of NESP®

6. No dose difference in achieving Hgb
levels in patients:
Not on dialysis
HD/PD Patients
6
IV versus SC routes

7. Adverse Effects
Comparable between
Darbepoetin and Epoietin
7
Adverse Effects

8. DPO VS EPO : NO SIGNIFICANT
DIFFERENCE IN CLINICAL OUTCOMES
Follow-up time, Number of Events, Incidence Rates, and Hazard
Ratios; Incident Patients in Hemodialysis Centers Using Darbepoetin
Alfa vs Epoetin Alfa

9. Adverse Effects
9
Change in LVMI

10. Adverse Effects
10
Change of QOL Scores

11. Effect on Iron
• By suppressing hepcidin level, there is
increased iron enteral absorption and
release of iron from the liver and
reticuloendothelial systems making it
available for erythropoiesis
• May prevent the harmful effect of excess
iron stores
11

13. Weighing the options

14. Assessment of new drugs
Health Services Research
• Policy Research • Access • Structure of Care
Clinical
• Efficacy
• Safety
• Impact on
natural course of
disease
Economic
• Cost analysis
• Cost-of-illness
• Cost-minimization
• Cost-benefit
• Cost-effectiveness
• Cost-utility
Humanistic
• Health related
quality of life
• Patient
satisfaction
• Caregiver impact
• Patient
preferences
• Functional status

15. Perspectives
CHOICE
PATIENT
-Clinical cure
-Quality of life
-Out-of-pocket costs
-Satisfaction with
treatment
PHYSICIANS/HOSPITALS
-Clinical cure
-Safety
-Clinical Cost
-Operational Costs
-Profit
3rd PARTY PAYER
-Clinical cure
-Cost
-Customer perception
of value
SOCIETY
-Clinical cure
-Cost
-Productivity

16. Medications used in treating anemia in CKD patients
Rasu R. et al. (2008). Curr Med Res Opin, 24(1), 129–137

17. Philippine Setting
Generic Name Brand Name Approved Initial
Dose
Average price (Php)
per unit/ug/mg
ESA
•Epoietin alpha [IV/SC] Eprex 50-100 units/kg P 0.275 /unit
•Epoietin beta [IV/SC] Recormon 50-100 units/kg P 0.352 /unit
•Darbepoietin alpha [IV/SC] Nesp 0.45 ug/kg P 99.025 /ug
P 0.282 (1ug:350unit)
P 0.148 (1ug:670unit)
Iron/FA Supplements
•Ferrous sulfate [oral] 200 mg elemental Fe P 0.004 /mg
•Iron sucrose [IV] 100 mg P 3.8/mg
•Folic acid [oral] 5 mg P 1.4/mg
Blood products
•Packed RBC + processing P 1000-5000 /bag
MIMS Drug Reference Philippines 2017 Issue 1
Mercury Drug Price 2017

18. Philippine Setting
MIMS Drug Reference Philippines 2017 Issue 1
Mercury Drug Price 2017
Epoeitin-alfa Darbepoetin-alfa
4000u SQ 3x/per week 40ug 1x/week
Php 2,140/vial x3
= Php 6,420/week
Php 3980.50/vial x1
= Php 3980.50/week
Epoeitin-beta Darbepoetin-alfa
5000u SQ 2x/per week 30ug 1x/week
Php 1760/vial x2
= Php 3520/week
Php 2980.50/vial x1
= Php 2980.50/week
38% savings
per week
(Php 2440)
15% savings
per week
(Php 540)

19. Cost-effectiveness Plane
Duhovny, D et al (2011) . NeoReviews, 12(2), e69–e75.

20. Cost-effective Drug
• An intervention is considered ‘cost-effective’
if the Incremental cost-effectiveness ratio
(ICER), compared to a current gold standard
treatment, falls below a given willingness to
pay (WTP) threshold specified for each
country.
Palmer, AJ. (2005). Nephrol Dial Transplant, 20, 1038–1041.

21. WTP Thresholds
• “WTP” refers to the amount a payer is willing
to pay for an improvement in patient
outcome, and represents a threshold above
which it is unlikely that a new intervention
would be regarded as good value for money.
Palmer, AJ. (2005). Nephrol Dial Transplant, 20, 1038–1041.

22. Cost-effectiveness Plane
Palmer, AJ. (2005). Nephrol Dial Transplant, 20, 1038–1041.

23. Cost-effectiveness: Egypt Experience
• A long-term five-year cost-utility model study
initiated by the country’s Pharmacoeconomic unit
• Studied HD patients insured by the Egyptian health
care system
• Compared Darbepoetin alfa and Epoetin alfa in
treatment of anemia in HD patients to target levels
• Measured direct medical costs including the cost of
therapy, and the cost of AEs treatment, cost of
hospitalization, lab tests done for monitoring
• Outcome: Quality adjusted life years (QALY)
Fouad, S. (2016). Value in Health, 19(7), A589

24. Cost-effectiveness: Egypt Experience
Total Costs
(EGP)
QALY
Epoetin alfa 512,145 17.711
Darbepoetin alfa 356,112 18.013
ICER -516,501 EGP/QALY gained
Fouad, S. (2016). Value in Health, 19(7), A589

25. Cost-effectiveness Plane
Darbepoetin for Maintaining
Haemoglobin Target Level versus Epoetin
in Hemodialysis Patients in Egypt

26. Dose Reduction = Dose Saving
Using an initial 200:1 conversion ratio, from epoetin to darbepoetin,
a subsequent reduction in dose was observed and an average 30%
dose savings was achieved Bonafont, X. et al. (2009). NDT Plus, 2(5), 347–353.

27. Cost Reduction: Epoetin IV to
Darbepoetin IV
Woodland, AL et al. (2017). Canadian Journal of Kidney Health and
Disease, 4, 205435811771646

28. Cost Reduction: Epoetin IV to
Darbepoetin IV
Time
Mean dose
conversion ratio
End of run-in phase 280:1
3 months 360:1
6 months 382:1
Woodland, AL et al. (2017). Canadian Journal of Kidney Health and
Disease, 4, 205435811771646

29. Cost Reduction
•A cost advantage for
EPO is not expected
unless the observed
EPO:DA dose
conversion ratio falls
below 150:1
•Darbepoetin has a
definitive lower weekly
cost at dose conversion
ratios greater than
275:1.
Woodland, AL et al. (2017). Canadian Journal of Kidney Health and
Disease, 4, 205435811771646

30. “Other” Costs
Burnier, M. et al. (2009). Journal of Medical Economics, 12(2), 77–86.

31. Clinical efficacy translated to
decreasing costs
Carrera, F and Burnier, M. (2009). NDT Plus, 2, 9–17.

32. Philippine Setting
rHuEPO Darbepoetin alpha
Baseline 1 month 3 months 6 months
Mean weekly dose 11,081 units 50 ug 39 ug 35 ug
Mean
dose/patient/month
44,324 units 202 ug 157 ug 141 ug
Mean drug
cost/patient/month
Php 24,150.04 Php 21,793.88 Php 17,125.75 Php 15,384.06
Mean nursing
cost/patient/month
Php 119.87 Php 42.38 Php 29.66 Php 33.90
Mean total
cost/patient/month
Php 24,269.91 Php 21,836.26 Php 17,155.42 Php 15,417.96
Savings/difference Php 2,433.65 Php 7,114.49 Php 8,851.95

33. “Other” Costs
Burnier, M. et al. (2009). Journal of Medical Economics, 12(2), 77–86.

34. Operational Costs: Storage
ESPO® NESP®
Space for 2weeks’ ESA to 100 patients
72% reduction

35. Operational Costs: Waste Disposal
NESP®
ESPO®
Disposal volume of ESPO and NESP
-100 patients for one week-

36. Work related mistakes =
Additional Costs

37. Work related mistakes =
Additional Costs

38. “Other” Costs
Mean Cost/
patient/year
in €
Mean Cost/
patient/year
in ₱
%
reduction
Pharmacy labor 10.1 611.46 39%
Dialysis unit labor 66.0 3,995.67 65%
Dialysis unit materials 4.11 248.82 61%
Waste unit materials 0.43 26.03 49%
Burnier, M. et al. (2009). Journal of Medical Economics, 12(2), 77–86.

39. Perspectives
CHOICE
PATIENT
-Clinical cure
-Quality of life
-Out-of-pocket costs
-Satisfaction with
treatment
PHYSICIANS/HOSPITALS
-Clinical cure
-Safety
-Clinical Cost
-Operational Costs
-Profit
3rd PARTY PAYER
-Clinical cure
-Cost
-Customer perception
of value
SOCIETY
-Clinical cure
-Cost
-Productivity