Post on 07-Apr-2018
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BioSimilaresPor qu S?
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2BioSimilares - Por qu S?
Coste
Acceso
Aspectos regulatorios
Similaridad Clnica
Futuro
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3BioSimilares - Por Qu S?
Coste
Acceso
Aspectos regulatorios
Similaridad Clnica
Futuro
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Figure 1:Average relative price of generic to brand by number of generic competitors
Generic Competition and Drug Prices
LD
Number of Generic ManufacturersSource: FDA analysis of retail sales data from IMS Health, IMS National Sales
Perspective (TM), 1999-2004, extracted February 2005.
http://aspe.hhs.gov/sp/reports/2010/GenericDrugs/longdesc.shtmlhttp://aspe.hhs.gov/sp/reports/2010/GenericDrugs/longdesc.shtml8/6/2019 Burg Biosimilares Por Qu S
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7Biotech drugs have solid efficacy, but access is limitedeven in Western markets
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3
20
20
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% of US patients treated 2008
Avastin Colorectal cancer 55-71% increase in progression-free survival 1
Herceptin Breast cancer (HER2+)33-52% reduced risk ofrecurrence 3
Erbitux Colorectal cancer 40% reduced risk of progression 5
Erbitux Head and neck cancer70% increase in progression freesurvival
Humira Moderate/severe RA Double the ACR response rate 6
Enbrel Moderate/severe RA Double the ACR response rate 6
1 -first and second line metastatic patients 2- first line HER2- patients3 - HER2+ patients 4 - Diffused Large B-Cell Lymphoma patients5 wild type KRAS patients 6 - ACR response criteria
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National Institute for Health and Clinical Excellence (NICE) rejections, by cost per quality-adjusted lifeyear.
McCabe C et al. Ann Oncol 2008;20:403-412
The Author 2008. Published by Oxford University Press on behalf of the European Society forMedical Oncology. All rights reserved. For permissions, please email:ournals. ermissions oxford ournals.or
90% of the present Biologic sales are exposed to Biosimilar entry
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93
17
45
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86
All Biologics Patents expired
2009 or earlier
Patents expiring
2010-2015
Patents expiring
2016-2020
Biosimilar
opportunity
Large opportunity
New affordabletreatment optionsfor more patients
Global biotech drug sales, $ bn, 2009
90% of the present Biologic sales are exposed to Biosimilar entryin the next 10 years. How will this affect the average cost oftreatment?
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10BioSimilares - Por Qu S?
Coste
Acceso
Aspectos regulatorios
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Futuro
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11Regulatory framework - EU
To date, > 10 products approved following the Biosimilar approval pathway
Draft Guideline on MAbs Specfic MAb guidelines expected
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12Regulatory framework - US
6/23/201112
Until recently, no regulatory path for approving biosimilarsexisted in the US as a result, biosimilars were submittedas new biological drugs (BLA).
The Healthcare Reform Act of March 2010established a framework for the approval of biosimilars.
FDA is charged with translating the general frameworkinto specific guidelines for the approval of biosimilars.
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13Biosimilars approved in EU
Somatropin Sandoz/Biopartners 2006
Epoetin alfa Sandoz/Hexal/Medice 2007
Epoetin zeta Stada/Hospira 2007
Filgrastim Teva/Ratiopharm/CT Arzneimittel/Hexal/Sandoz 2008/2009
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14BioSimilares - Por Qu S?
Coste
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Aspectos regulatorios
Similaridad Clnica
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15What is a BioSimilar - the definition
A BioSimilar is a biopharmaceutical that is
- physically,- chemically,
- biologically, and- clinically
similar to an approved biological reference product
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16Why similar and not identical ?
6/23/201116
Biotech drugs arecomplex / large
molecules
Manufactured drugs mayvary slightly* from the
drug that was originallyapproved
As aresult
for example: batch
to batch variation isoften observed forany innovators drug
Slight variations do notaffect efficacy and
safety as long as theyare within
well-defineproduct specifications
and themanufacturingprocess is well
controlled
* In drug structure and physico-chemical profile
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17Biotech drugs are protein-based medicines
Herceptin ParacetamolInsulin
Large and complex molecules
Produced by biological systems rather than chemical synthesis
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18
H Bi Si il d l d
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19How are BioSimilars developed process
6/23/201119
First step Second step
Establish a
production processthat yields a product that iscompletely consistent with
- physical- chemical- biological
product specifications of thereference drug
Confirm comparability:
-Pre-clinical studies
-Clinical studies(PK / PD / efficacy)
E l T ti (Bi Si il GCSF)
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Example of one of the comparability parameters:fluorescent spectroscopy
Example: Tevagrastim (BioSimilar GCSF)
First step:
Establish aproduction processthat yields aBioSimilar product
(Tevagrastim) thatis completelyconsistent with theproductspecification of theinnovatorsreference product
(Neupogen)Tevagrastim
Neupogen
E l T ti (Bi Si il GCSF)
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Example: Tevagrastim (BioSimilar GCSF)
Second step:
Confirm similarity by pre-clinical and clinical testing against the innovators molecules
5 g/kg (Tevagrastim)
5 g/kg (Neupogen)
10 g/kg (Tevagrastim)
10 g/kg (Neupogen)
Pharmacokinetics*
* GCSF (filgrastim) blood levels in healthy volunteers receiving a single injection
22E ample Te agrastim (BioSimilar GCSF)
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Second step:
Confirm similarity by pre-clinical and clinical testing against the innovators molecules
Example: Tevagrastim (BioSimilar GCSF)
5 g/kg (Tevagrastim)
5 g/kg (Neupogen)
10 g/kg (Tevagrastim)
10 g/kg (Neupogen)
Pharmacodynamics*
* Change in Average Neutrophil Count following a single injection of GCSF in healthy volunteers
23Example: Tevagrastim (BioSimilar GCSF)
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Second step:
Confirm similarity by pre-clinical and clinical testing against the innovators molecules
Example: Tevagrastim (BioSimilar GCSF)
Efficacy* TevagrastimNeupogen
Placebo
* Cancer patients receiving chemotherapy in day 1. GCSF is administered daily. Efficacy measure: duration of severe neutropnia(average neutrophil count below 0.5 x 10^9)
24Example: Tevagrastim (BioSimilar GCSF)
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Example: Tevagrastim (BioSimilar GCSF)
Chemo. Induced neutropenia
Bone marrow transplantation
Severe chronic neutropenia
Neutropenia in HIV patients
Stem cell mobilization
In September 2008, based on comparability data provided by Teva,
EMA recognized Tevagrastim as a BioSimilar to Amgens Neupogen
Tevagrastim was the first BioSimilar GCSF to be approved in the EU
EMA granted Tevagrastim the entire scope of indications of Neupogen:
Physicalsimilarity
Chemicalsimilarity
Biologicalsimilarity
Clinicalsimilarity
(in relevantsetting)
Chemotherapyinduced
neutropenia
extrapolation
comparability data Indications granted
+ ++
25Example: TL011 Biosimilar to Rituximab
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Example: TL011 - Biosimilar to Rituximab
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27Example: TL011 - Biosimilar to Rituximab
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Rituximab Clinical Studies
Example: TL011 - Biosimilar to Rituximab
28Rituximab Biosimilar Studies
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28Rituximab Biosimilar Studies
Teva Phase I/II in RA. Phase I in NHL
Sandoz Phase I and Phase II in RA
HospiraPhase I in RA
SpectrumViropro
No details
Clincaltrials.gov, corporate press releases
Limited information due to confidentiality
29Rituximab Biosimilar Studies
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Rituximab Biosimilar Studies
Clincaltrials.gov,
30Rituximab Biosimilar Studies
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Rituximab Biosimilar Studies
Clincaltrials.gov, corporate press releases
To date, > 200 patients for RA and >200 for NHL in Phase I/II studies planned
Several thousands for Phase III?
RA bridging for NHL?
At least 5 companies are developing a Rituximab BioSimilar
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BioSimilares Por Qu S?
Coste
Acceso
Aspectos regulatorios
Similaridad Clnica
Futuro
32Future of Biosimilars
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Clincaltrials.gov, corporate press releases
Similarity proved in ClinicalTrials and Practice
Current requirements
Similarity NOT proved inClinical Trials
Simplerrequirements
Lower entrybarriers
Current/Increasedrequirements
Increasedrequirements
Higher entrybarriers
33Generic price and competition
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p p
Clincaltrials.gov,
Could unavailability of affordable Biologics lead to significant change in legislation?
34BioSimilares - Por Qu S?
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Nuestros sistemas de salud exigen frmacos de precio acequible
La EMEA y otras autoridades garantizan la calidad, seguridad y eficacia de los Biosimilares
Ensayos Clnicos extensos
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Moltes gracis