Download - Foro de genéricos y biosimilares
Genéricos y biosimilares en la práctica médica
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA - Medellín, ColombiaBogotá – 08/2016
@Onconerd
@onconerd
Mauricio Lema: Conflicto de interés
Honorarios por conferencias (2015): Roche, Novartis, MSD, Aztra-Zeneca, AMGEN, Pfizer, Boheringer-Ingelheim
1. No estaríamos hoy aquí si los medicamentos innovadores fueran baratos
Precios de los agentes nuevosMedicamento Dosis Precio/mg (US$) Costo mediano (US$)
Nivolumab 3 mg/kg 28.78 103.220 (Melanoma)Pembrolizumab 2 mg/kg - 150.000 (Melanoma)Ipilimumab 3 mg/kg 156.46 158.282 (Melanoma)
Palbociclib 125 qd x21/28d 3.75 118.090 (Mama)
Blinatumomab 28 mcg/kg/d 9000 178.000 (ALL)
Ramucirumab 8 mg/kg q15d 10.2 159.000 (Colon)
http://www.medscape.com/viewarticle/845707 - http://www.medscape.com/viewarticle/839171#vp_1http://www.medscape.com/viewarticle/836879http://www.pharmacytimes.com/publications/health-system-edition/2015/march2015/cyramza-by-eli-lilly-and-companyhttp://www.medscape.com/viewarticle/831150http://www.medscape.com/viewarticle/830145http://www.medscape.com/viewarticle/830145http://www.medscape.com/viewarticle/828882
Oro: US$ 0.036/mg
Medicamento Dosis Precio mes ($US) Costo mediano (US$)
Crizotinib 250 mg bid 11.500 138.000/año
Ceritinib 750 mg/d 13.200 158.000/año
Precios de los agentes nuevosMedicamento Dosis Precio/mg (US$) Costo mediano (US$)
Nivolumab 3 mg/kg 28.78 103.220 (Melanoma)Pembrolizumab 2 mg/kg - 150.000 (Melanoma)Ipilimumab 3 mg/kg 156.46 158.282 (Melanoma)
Palbociclib 125 qd x21/28d 3.75 118.090 (Mama)
Blinatumomab 28 mcg/kg/d 9000 178.000 (ALL)
Ramucirumab 8 mg/kg q15d 10.2 159.000 (Colon)
http://www.medscape.com/viewarticle/845707 - http://www.medscape.com/viewarticle/839171#vp_1http://www.medscape.com/viewarticle/836879http://www.pharmacytimes.com/publications/health-system-edition/2015/march2015/cyramza-by-eli-lilly-and-companyhttp://www.medscape.com/viewarticle/831150http://www.medscape.com/viewarticle/830145http://www.medscape.com/viewarticle/830145http://www.medscape.com/viewarticle/828882
Aprobado en Colombia
Medicamento Dosis Precio mes ($US) Costo mediano (US$)
Crizotinib 250 mg bid 11.500 138.000/año
Ceritinib 750 mg/d 13.200 158.000/año
Genéricos
A generic medicinal product is a medicinal product which has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product (the innovator), and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies, thus supporting equivalent efficacy, unless the requirements for a Biowaiver have been satisfactorily fulfilled
Committee for Medicinal Products for Human Use, EMA, 2012
Generics can cost as much as 80–85% less than the original compound
Generic Drug Market: Growing and Merging. Lancet Oncol, 2015
According to IMS Health, in the US alone unbranded generic drugs accounted for 80% of prescriptions dispensed during the 2013 fiscal year
Generic Drug Market: Growing and Merging. Lancet Oncol, 2015
Prescription Share in the USRelative cost
2. El problema no es sólo económico, sino que se vuelve también un problema médico.
The extensive experience from bringing generic products to the market over the last decades allows the conclusion that they are well-accepted and provide a useful alternative option for cost-effective pharmacotherapy.
Borg JJ, Sci Pharm, 2014
InnovadorGenérico A
Genérico BBiod
ispon
ibili
dad
acep
tabl
e
FenitoínaCarbamazepinaÁcido valproico
LamotriginaLevetiracetam
Topiramato
LevodopaClopidogrel
Burkhardt RT Neurology. 2004;63:1494–1496.Armstrong TS J Neurooncol. 2010;98:137–141. Gidal BE Curr Neurol Neurosci Rep. 2009;9:333–337. Berg MJ Neurology. 2008;71:525–530.Bautista RE Epilepsy Res. 2011;95:158–167.Andermann F Epilepsia. 2007;48:464–469. LeLorier J Neurology. 2008;70:2179–2186.Makus KG Clin Ther. 2007;29:334–341.Talati R Pharmacotherapy. 2012;32:314–322. Duh MS Neurology. 2009;72:2122–2129.
Gasser UE BMC Pharmacol Toxicol. 2013;14:24
Impact on Bacterial Resistance of Therapeutically Nonequivalent Generics: The Case of Piperacillin-
Tazobactam
We studied a generic product of piperacillin-tazobactam characterized by pharmaceutical and pharmacokinetic equivalence but a faulty fit of Hill’sEmax sigmoid model that could be interpreted as pharmacodynamic nonequivalence
Rodríguez CE, PLoS One, 2016
Generic Vancomycin Enriches Resistant Subpopulations ofStaphylococcus aureus after Exposure in a Neutropenic Mouse Thigh Infection Model
The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide.
Rodríguez CE, Amtimicrob Agents Chemother, 2012
Resistance Frequencies with innovator and generics
Pharmacodynamics of nine generic products of amikacin compared with the innovator in the neutropenic mouse
thigh infection model
As we demonstrated previously with other antibiotics such as vancomycin, gentamicin and oxacillin, the generic products of amikacin failed the in vivo efficacy testing. The therapeutic equivalence should be assessed in vivo before clinical approval of generic products.
Zuluaga A, BMC Res Notes, 2015
Generic ImatinibA Multi-centric Bioequivalence Trial in Ph+ Chronic Myeloid Leukemia Patients to Assess Bioequivalence and Safety Evaluation of Generic Imatinib Mesylate 400 mg Tablets
Both formulations were well tolerated after oral administration of IMPs.
Failure of copy Imatib (CIPLA, India) to maintain hematologic and cytogenetic responses in chronic myeloid leukemia in chronic phase.
This case report suggests a difference in clinical efficacy between the authorized form of imatinib (Glivec) and the copy version of the drug (Imatib)
Arora R, Cancer Res Treat. 2016 Mattar M Int J Hematol, 2010
The Introduction of Generic Aromatase Inhibitors and Treatment Adherence
Among Medicare D EnrolleesLIS: Lower-income subsidy
The introduction of generic medications attenuated the decline in adherence to AIs over three years of treatment among breast cancer survivors not receiving low-income subsidies
Neuner J, JNCI, 2015
The extensive experience from bringing generic products to the market over the last decades allows the conclusion that they are well-accepted and provide a useful alternative option for cost-effective pharmacotherapy.
Borg JJ, Sci Pharm, 2014
Sé que algunos son aceptables, pero no tengo manera de saber cuáles…
Conclusiones preliminares
• La adopción de medicamentos genéricos puede traer beneficios económicos y en adherencia.
• Algunos medicamentos genéricos son eficaces y seguros.
• Otros no.• En Colombia existen DEMASIADOS que no lo son.• No tenemos herramientas confiables para separar los
unos de los otros.• Existe un clima de desconfianza e incertidumbre que
afecta la credibilidad de todos los involucrados
Biosimilares
Front Pharmacol. 2016 Jun 29;7:193.
Oportunidades de los
biosimilares
Alterntiva terapéutica
Expansión del uso de
biológicos
Mejor acceso para los
pacientes
Libera recursos en salud para
otros menesteres
Ahorros y eficiencias en el costo en salud
Front Pharmacol. 2016 Jun 29;7:193.
INN Reference Exclusivityexpiration EU
Biosimilar Year of EMA approval
Infliximab Remicade 2015 1999
Inflectra 2013
Remsima 2013
Adalimumab Humira 2018 2003
Etanercept Enbrel 2015 2016
Benepali 2016
Rituximab Rituxan 2013 1998
Trastuzumab Herceptin 2014 2000
Bevacizumab Avastatin 2022 2005
Cetuximab Erbitux 2014 2004
Ranibizumab Lucentis 2022 2007
3. Los medicamentos biológicos no son copiables.
Pure Red-Cell Aplasia and Antierythropoietin Antibodies in Patients Treated with Recombinant
Erythropoietin
Casadevall N, NEJM, 2002
Neutralizing antierythropoietin antibodies and pure red-cell aplasia can develop in patients with the anemia of chronic renal failure during treatment with epoetin
Trastuzumab + Paclitaxel.
2001
Phase III
Trastuzumab + Docetaxel
2005
Lapatinib + Capecitabine
2006Phase III
Slamon DJ, et al. (2001) N Engl J Med 344:783–792.Marti M, et al. J Clin Oncol 23:4265–4274.Geyer, et al. NEJM, 2006 Baselga, et al. NEJM, 2012Verma, et al. NEJM, 2012
1st-line
Current 1st- and 2nd-line therapies in Her2+ MBC
Pertuzumab +Trastuzumab +
Docetaxel2012
T-DM12012
2nd--line
Phase IIICLEOPATRA
Phase IIIEMILIA
Puede el biosimilar de trastuzumab combinarse con el pertuzumab?
35
Genentech Confidential—Internal Use Only
Anatomy of an Antibody-Drug Conjugate (ADC)
Antibody targeted to tumor
Very potentchemotherapeutic drug• Tubulin polymerization inhibitors
• Maytansines (DM1, DM4)• Auristatins (MMAE, MMAF)
• DNA damaging agents• Calicheamicins• Duocarmycins• Anthracyclines (doxorubicin)
• Humanized monoclonal Ab (IgG1)
• mAb with Fc modifications (modulate ADCC, CDC activity)
• Other mAb fragments
36
Linker stable in circulation
• Linker biochemistry• Acid labile (hydrazone)• Enzyme dipeptides (cleavable) • Thioether (uncleavable)• Hindered disulfide (uncleavable)
• Site of conjugation• Fc, HC, LC
4. Los biosimilares pueden ser adoptados siempre y cuando cumplan todos los pasos que demuestren su eficacia y seguridad
“Innovar” en la forma de evaluar la eficacia y seguridad de biosimilares puede ser potencialmente fatal para los pacientes…
En Colombia se exige más que en otros
países para registrar medicamentos
innovadores
En Colombia se exige menos que en otros países para registrar
medicamentos genéricos / biosimilares
En mi país no dejan entrar las drogas innovadoras, pero piensan admitir biosimilares con estándares no aceptables en países civilizados…
Conclusiones• Los medicamentos genéricos y biosimilares pueden ser
alternativas de tratamiento cuando se demuestra que tienen eficacia y seguridad comparables con los innovadores.
• Las entidades regulatorias deben ser al menos tan exigentes con estos medicamentos no-innovadores a como lo son con los innovadores, y no al revés como se viene practicando.
• Las soluciones inmediatistas del problema económico que se suscita del avance de la medicina implican que algunos pacientes no van a tener acceso a medicamentos de buena calidad o innovadores, y ambas situaciones inaceptables para un país que se jacta de cuidar a sus ciudadanos, y son inaceptables como médico.
“Una conferencia consiste en un combate cuerpo a cuerpo
con los minutos”
José Ortega y Gasset, Vives, 1940
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