Biosimilari: Epoetine in Nefrologia. Arrigo Schieppati AO Papa Giovanni XXII, Bergamo 21 Aprile 2015

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1 Biosimilari: Epoetine in Nefrologia Arrigo Schieppati AO Papa Giovanni XXII, Bergamo 21 Aprile 2015

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3 Paul Carnot

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5 AJ Erslev. Blood, 1974

6 Anemia in CKD The anemia of chronic kidney disease (CKD), if severe and left untreated, can result in deterioration in cardiac function decreased cognition and mental acuity debilitating symptoms Observational studies have also suggested an association of renal anemia with an increased risk of morbidity and mortality

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8 The Effect of EPO Given 3 Times a Week at 150 U/Kg Eschbach JW et al. N Engl J Med 1987;316:73-78.

9 ESA development Epoetin Epoetin Darbepoetin Epoetin Methoxy PEG-epoetin Fishbane S. Curr Opin Nephrol Hypertens 2009;18: Macdougall IC & Ashenden M. Adv Chron Kid Dis 2009;16:

10 Erythropoietin-stimulating agents (ESAs) are highly effective in treating the anemia of CKD They have: reduced the need for red cell transfusions less viral infections, less allosesitization helped mobilize iron stores less hemosiderosis ameliorated anemia-induced symptoms

11 The Anaemia Working Group of ERBP maintains its view that Hb values of g/dl should be generally sought in the CKD population without intentionally exceeding 13 g/dl and that the doses of ESA therapy to achieve the target haemoglobin should also be considered. ERBP 2010

12 The correction to normal levels of Hb with ESAs is not usually recommended in people with anaemia of CKD Typically maintain the aspirational Hb range between 10 and 12 g/dl for adults, young people and children aged 2 years and older, KDIGO 2011

13 In general, we suggest that ESAs not be used to maintain Hb concentration above 11.5 g/dl (115 g/l) in adult patients with CKD KDIGO 2012

14 ESA side-effects ESA therapy is associated with a number of significant side effects, including adverse cardiovascular events with higher hemoglobin levels pure red cell aplasia hypertension. A variety of factors may cause patients to be relatively hyporesponsive to EPO

15 More ESA on the market Epoetin Epoetin Darbepoetin Epoetin Methoxy PEG-epoetin Biosimilar epoetins Fishbane S. Curr Opin Nephrol Hypertens 2009;18: Macdougall IC & Ashenden M. Adv Chron Kid Dis 2009;16:

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17 Sorgel et al. BMC Clinical Pharmacology 2009

18 Sorgel et al. BMC Clinical Pharmacology 2009

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23 Impiego di un ESA biosimilare in un centro dialisi satellite Abbiamo condotto una prima esperienza nell impiego di un ESA biosimilare su 22 pazienti stabili seguiti presso un centro dialisi satellite Sono stati analizzati tre periodi di 6 mesi negli anni

24 Risultati di questa esperienza pilota Mantenimento del target di Hb con dosi variabili di biosimilare ed una media di circa 300 UI per mcg di darbepoetina Nessun effetto collaterale, né problemi organizzativi maggiori Costi notevolmente ridotti

25 Nel Novembre 2011 abbiamo deciso di iniziare la terapia con ESA biosimilare nei pazienti dializzati al Centro ospedaliero

26 Hb in emodializzati trattati per sei mesi con Darbopoetina o con Biosimilare Hb (g/dl) 12 Darbo Biosim Mesi di trattamento 5 6

27 Pazienti che sono nel target di Hb durante il trattamento Darbo Biosim 100 Al target (%) Mesi di trattamento 6

28 Pazienti con Hb < 10 g/dl Darbo Biosim 20 % Mesi di trattamento 5 6

29 Pazienti con Hb > 12 g/dl Darbo Biosim 40 % Mesi di trattamento 5 6

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31 Penetrazione delle EPO Biosimilari 35 % di penetrazione Giappone Francia Italia Spagna Germania Gran Bretagna

32 TYPE OF ESA : We recommend choosing an ESA based on the balance of pharmacodynamics, safety information, clinical outcome data, costs, and availability. (1D) : We suggest using only ESAs that have been approved by an independent regulatory agency. Specifically for copy versions of ESAs, true biosimilar products should be used. (2D)

33 Comparisons of ESAs Discuss the choice of ESA with the person with anaemia of CKD when initiating treatment and at subsequent review, taking into consideration the patient's dialysis status, the route of administration and the local availability of ESAs. There is no evidence to distinguish between ESAs in terms of efficacy.

34 Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis In the CKD setting, there is currently insufficient evidence to suggest the superiority of any ESA formulation based on available safety and efficacy data. Directly comparative data for the effectiveness of different ESA formulations based on patient-centred outcomes are sparse and poorly reported and current research studies are unable to inform care. All proprietary ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, and methoxy polyethylene glycol-epoetin beta) prevent blood transfusions but information for biosimilar ESAs is less conclusive. Cochrane Database Sys Rev, 2014

35 A significant question for policy makers and funding bodies will be whether the cheaper, biosimilar agents can be used in place of expensive, established brands of ESA. The meta-analysis is not able to answer that question definitively because the clinical trial evidence for the biosimilars is not as robust as it is for the proprietary agents. Cochrane Database Sys Rev, 2014

36 We need further head-to-head trials of biosimilar ESAs versus the more established agents to prove that they are as safe and as effective. Unfortunately, without economic imperative, such trials are unlikely to be conducted. Cochrane Database Sys Rev, 2014