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Biosimilars:
Providing More Treatment Options
By Leala Thomas

By 2020 the worldwide market for biologics is expected to exceed $390 billion (up from $46 billion in 2002)
and account for 28% of the global pharmaceutical market. As they are developed across a wider rangeof therapeutic areas, biosimilars will play a more important role by providing a greater choice of treatment
options (Aitken 2016).
Worldwide access to biologics is a real issue due to their
exorbitant cost. In developing countries with limited resourcesthat primarily focus on fatal diseases, there may not becoverage for biologics for their population. In more than 50%
of European countries the annual cost of a biologic exceeds
their per capita GDP by up to 11 times.
It is hoped that the development of biosimilars will lead to morecompetition, and therefore, more accessible, cost-effectivetreatments. While there are challenges in making biosimilars, thetimeline for their development is approximately five years less thanthat for an originator biologic. Biosimilars can offer cost savings
from 10–30% over biologics and their availability allows better
access to newer therapies (Lorenzetti 2015).
Current Opportunity for Biosimilars
Several high-priced biologics (worth $81 billion) are approachingpatent expiration, providing an opportunity for manufacturers
to develop more affordable biosimilars. The eight top-selling
biologics losing patent exclusivity across Western Europe andthe U.S., an equivalent of $56 billion, focus on two major therapy
areas, inflammation and diabetes, and include adalimumaband etanercept for rheumatoid arthritis (RA), Crohns’ disease,
psoriasis, and other inflammatory diseases and insulin glargine fortype I and II diabetes.

Case Study: The Global Impact of RA
About 1% of the global population is affected by RA. It
primarily afflicts women, mostly between the ages of 30 and55, during their most productive adult years. It’s a chronic
condition in which the immune system attacks the lining of
the joints causing swelling, stiffness, and pain. If RA is left
untreated, it can lead to irreparable joint damage (Figure 1).
Up to 40% of RA patients stop working within five yearsof diagnosis due to increasing disability. In addition to theconstant pain, fatigue, and deformity, patients are at greaterrisk of developing cardiovascular disease, infections, andmental health disorders. The risk of mortality is also doublethat in the normal healthy population (American College ofRheumatology 2017). Fortunately, there are some encouraging
advances in therapeutic treatment for RA patients.

Thickened synovial
membraneSynovial fluid
Degradedcartilage

Fig. 1. Effect of rheumatoid arthritis on a joint.

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Biosimilars in RA Treatment
Fifteen years ago, the treatment objective for RA was tobalance the deterioration from poorly controlled disease
with the long-term side effects of corticosteroid use. In
recent years, the introduction of biologics such as rituximab,adalimumab, and etanercept have revolutionized RA care
(Table 1). Between 30 to 70% of patients who do not benefit
from first-line medications experience some measure ofrelief from biologics. Roughly 40% of patients don’t respondto the first biologic they try and switch to another biologic(Consumer Reports 2013). While these biologics are used

to treat symptoms, they are not a cure. In addition, they arevery expensive, costing in excess of $5,000 per week, andcause their own side effects. Some fortunate RA patients
have achieved remission on a biologic and have even beenable to sustain it after drug reduction or cessation. Althoughbiologics are not a perfect solution for RA patients, theiradoption has marked a huge improvement in outcomes.
However, more options are needed and the introduction andcontinued research in biosimilars could provide these options
for patients.

Table 1. Therapeutics available for rheumatic diseases.
Type

Originator BiologicBiosimilars

Composition

DeliverySide Effects

Tumor Necrosis
Factor (TNF)
inhibitor

Etanercept

CHS-0214
GP2015
HD203
SB4Fusion protein, the IgG
antibody is fused to a TNF
inhibitor

Self-injection

Serious infections

TNF inhibitor

Adalimumab

ABP 501
BI 695501
CHS-1420
GP-2017
M923
SB5
ZRC-3197

Human monoclonal antibody(mAb)

Self-injection

Serious infections

TNF inhibitor

Infliximab

BOW015CT-P13
PF-06438179
SB2Part human, part mouse mAb

IV administered for 2 hr,
3 times/week for 6 weeks,then every 8 weeks

Serious infectionsInterleukin-6 (IL-6)
blocker

Sarilumab

N/A

Human mAb

Injection every 2 weeks

Infection, increase in liver
enzymesIL-6 blocker

Tocilizumab

N/A

Human mAb

IV administered over 1 hr,once/month

Infection, increase in liver
enzymes

B-cell targeter

Rituximab

CT-P10GP2013
PF-05280586

Part human, part mouse mAb

Two 4–6 hr infusions, 2 weeks
apart, every 6–12 months

Infection, infusion reaction
consisting of itching, rash,wheezing

IL-1 blocker

Anakinra

N/A

Man-made form of IL-1
receptor antagonist

Self-injected once/day

Infection

Janus kinaseinhibitor

Tofacitinib

N/A

Small molecule drug

Oral

Increased liver enzymes,cholesterol, risk of shingles

Data from Arthritis Foundation 2017 and Dorner et al. 2016.

Currently, over 20 biosimilars targeted to the RA patient
population have become available on the market in more than
70 countries. In addition, the pipeline has over 700 biosimilars
in preclinical and clinical trial development for use in rheumatic
diseases (Dorner et al. 2016).
Continuing Clinical Concerns
In order to obtain regulatory approval, the FDA, EMA,
and other regulatory bodies require a pharmacokinetics/
pharmacodynamics (PK/PD) study and at least one
randomized clinical trial (RCT) to show efficacy,
immunogenicity, and comparable safety of the biosimilar whencompared to its originator biologic. The confirmation RCT
needs to be designed using an equivalence margin comparing
primary endpoint differences between active treatment andplacebo statistically derived from a meta-analysis of previous
RCTs with the originator (Cohen and Kay 2017).

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Once a biosimilar is approved for use, there are some relevant
clinical concerns when transitioning from the originator
biologic. There are no publically available studies that discuss
manufacturing changes in the originator biologic althoughposttranslational differences do occur. Most RCTs studying
transitions to a biosimilar include only one randomized switch
after assessment of the primary endpoint. More than a decadeof experience in the European Union has demonstrated thattransitioning from the originator filgrastim to its biosimilar has
not lowered efficacy or increased adverse events. However,prescribers are still wary of transitioning patients from one
therapeutic to another without additional data. Two studies,NOR-SWITCH (sponsored by the Norwegian government) andPLANETAS (extended from the original PK/PD study of infliximab
in ankylosing spondylitis) are currently examining the issue oftransitioning. RA patients will continue to be important test
subjects for biosimilars because they allow researchers to obtaininsights into immunogenicity by measuring anti-drug antibodies.
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What Happens Next?
Biosimilars have now entered clinical practices globally forthe treatment of RA and other diseases. Limited experience,
mostly in the form of RCTs comparing one product toplacebo, indicates that biosimilars have similar efficacy andsafety profiles to their corresponding originator biologics.
Harmonizing regulatory guidelines and recommendations
for use will reduce concerns and increase usage. If the costsavings of biosimilars are realized, worldwide accessibility
will increase and usage will rise. This will provide patientsworldwide with RA, other autoimmune conditions, and manyother diseases a cost-effective improvement in treatment
options and enhanced quality of life.

References
Aitken M (2016). Delivering on the potential of biosimilar medicines: The role offunctioning competitive markets. iqvia.com/-/media/iqvia/pdfs/institute-reports/
delivering-on-the-potential-of-biosimilar-medicines.pdf, accessed December
27, 2017.
American College of Rheumatology (2017). Rheumatoid Arthritis. rheumatology.
org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis,
accessed December 27, 2017.
Arthritis Foundation (2017). Biologics overview. arthritis.org/living-with-arthritis/treatments/medication/drug-types/biologics/drug-guide-biologics.php,
accessed December 27, 2017.
Cohen S and Kay J (2017). Biosimilars: Implications for rheumatoid arthritis
therapy. Curr Opin Rheumatol 29, 260–268.
Consumer Reports (2013). Using biologic drugs to treat rheumatoid arthritis:
Comparing effectiveness, safety, side effects, and price. consumerreports.
org/cro/2013/03/using-biologic-drugs-to-treat-rheumatoid-arthritis/index.htm,
accessed December 27, 2017.
Dorner T et al. (2016). The changing landscape of biosimilars in rheumatology.
Ann Rheum Dis 75, 974–982.
Lorenzetti L (2015). Biosimilars may one day save your life. But what are
they? fortune.com/2015/02/06/biosimilars-what-are-they/, accessed
December 27, 2017.
Arthritis Foundation is a trademark of The Arthritis Foundation, Inc.

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