burg biosimilares por qué sí

8/6/2019 Burg Biosimilares Por Qu S

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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


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.shtml


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Coste

Acceso


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Futuro


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7Biotech drugs have solid efficacy, but access is limitedeven in Western markets

16

3

20

20

28

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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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9

93

17

45

24

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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Coste

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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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Coste

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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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21

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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 (Neupogen)

Pharmacokinetics*

* GCSF (filgrastim) blood levels in healthy volunteers receiving a single injection

22E ample Te agrastim (BioSimilar GCSF)


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22

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Second step:




5 g/kg (Neupogen)


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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23

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Second step:



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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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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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



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Rituximab Biosimilar Studies

Clincaltrials.gov,



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Rituximab Biosimilar Studies


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


Similaridad Clnica

Futuro

32Future of Biosimilars


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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?



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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

burg biosimilares por qué sí

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