Market Access tosupport productdi�erentiation

CMC innovatorand biosimilar

characterization

In vivostudies

ExpeditedPhase I and

Phase IIIclinicalstudies

Proactiveregulatory

strategy andagency

engagement

BIOSIMILARS FOR RHEUMATOID ARTHRITISAn Experienced Partner Can Foresee Your Biosimilar Development ChallengesThe market for the use of biosimilars in the treatment of rheumatoid arthritis is rapidly expanding as many high-profile therapies come off patent. Despite the increasing number of biosimilars, there remain clinical, regulatory and market access challenges for developers.

REGULATORY-COMPLIANT ANALYTICAL STRATEGIES FOR CELL BANKS, INTERMEDIATES, DRUG SUBSTANCES AND DRUG PRODUCTS

►Analytical and stability assay development, qualification and testing to GMP standards

►Assessment of biosimilarity to innovator drug, including characterization of process and analytical anomalies

►Management of reference standards and antibody reagents

►Refinement of the analytical control strategy

►Process validation testing and linkage to product CQAs

►Validation to ICH requirements and cGMP standards

►Manufacturing lot comparability testing

►Accelerated and long-term stability testing, including routine and global lot release to cGMP and ICH standards

►Monitoring and identification of data trends during commercialization

COVANCE: THE ONLY GLOBAL CRO WITH AN INTEGRATED APPROACH

RABIOLOGICPRODUCTSCURRENTLYTARGETEDBYBIOSIMILARSINDEVELOPMENT

Target product Company Estimated number of biosimilars in

development globally

Humira®

(adalimumab)AbbVie 13

Enbrel®

(etanercept)Amgen 6

Remicade®

(infliximab)Merck/Johnson

& Johnson13

Rituxan®

(rituximab)Roche 35

Source: Amgen 2015 Trends in Biosimilars Report

LIKELIHOODOFPAYERSSTEERINGUTILIZATIONTOWARDSBIOSIMILARS

Source: Covance Commercial Payer Survey 2013–2015

Will notsteer utilization

toward biosimilars

Very likelyto steer utilizationtoward biosimilars

1086420

Oncology 6.16

RA 7.60

Likelihood of steering utilization

All therapeutic areas 7.12

SOLVING BIOSIMILAR CHALLENGES WITH COVANCE INTEGRATED DEVELOPMENT SOLUTIONS

Covance has contributed to the development of 122 unique biosimilars in 217 individual projects since 2010, including 51 biosimilars directed against inflammatory targets (abatacept, adalimumab, aflibercept, belatercept,

etanercept, infliximab, omalizumab, rituximab, tocilizumab, ustekinumab)

Development challenges Covance solutions

CM

C ►Efficiently demonstrating analytical similarity to innovator

►Applying most appropriate testing procedures

►Tailored CMC strategy around linking biosimilar structure and function to likely clinical efficacy and risks to safety

PAT

IEN

T R

EC

RU

ITM

EN

T

AN

D R

ET

EN

TIO

N

►Competition to recruit required patients►Low investigator and patient interest in

biosimilar studies►Poor patient compliance►Poor patient retention in long studies

►Database of >1,200 investigators who have expressed interest in conducting biosimilar studies

►Xcellerate® Trial Design leverages data in the Covance clinical knowledgebase, which houses >40% of global trial data at any given time, providing the ability to locate high-performing investigators and target patient populations

►Strong relationship with the National Institutes of Health helps optimize recruitment and retention for studies based in the U.K.

►Providing patients and caregivers with ongoing drug administration training

►Continued patient education, phone call/text appointment reminders

DA

TA Q

UA

LIT

Y

►High placebo response rates – up to 30% in RA

►Subjective nature of trial outcomes, e.g., PRO

►Variability in objective endpoint data, e.g., imaging

►Reducing eligibility creep via robust study design and specialist training of site staff, e.g., in ACR20 assessments

►Using an ePRO device for direct data integration

►Centralized assessment of imaging data

RE

GU

LA

TOR

Y ►Lack of coherence between regulatory bodies

►Rapidly changing guidelines

►Early and frequent agency engagement by our regulatory experts that each have up to 30 years’ experience worldwide and strong relationships with the National Institute for Health Research (NIHR) Clinical Research Network

MA

RK

ET

A

CC

ES

S

►Low acceptance of new biosimilars with key stakeholders

►Challenging reimbursement policies

►Strategic planning from the early stages of development, considering all desired markets

►Generating real-world evidence to prove value of biosimilar

Covance has significant global experience employing realistic estimates, effective trial management and proactive risk mitigation to optimize your biosimilar drug development

Learn more about our drug development solutions at www.covance.comCovance Inc., headquartered in Princeton, NJ, USA is the drug development business of Laboratory Corporation of America Holdings (LabCorp). COVANCE is registered trademark and the marketing name for Covance Inc. and its subsidiaries around the world.

The Americas +1.888.COVANCE (+1.888.268.2623) +1.609.452.4440 Europe / Africa +00.800.2682.2682 +44.1423.500888 Asia Pacific +800.6568.3000 +65.6.5686588

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