Hope S. Rugo, MD, FASCO, prepared useful Practice Aids pertaining to biosimilars for this CME/MOC/CNE/CPE activity titled "Biosimilars as Partners in Oncology: Expert Guidance on Understanding and Incorporating Biosimilar Agents in Real-World Care." For the full presentation, monograph, complete CME/MOC/CNE/CPE information, and to apply for credit, please visit us at http://bit.ly/38DBgFb. CME/MOC/CNE/CPE credit will be available until April 27, 2021.

1. Access the activity, “Biosimilars as Partners in Oncology: Expert
Guidance on Understanding and Incorporating Biosimilar Agents
in Real-World Care,” at PeerView.com/BBG40
Biosimilars: What Are They?
PRACTICE AID
A Biosimilar Is a Biologic Product1
Biosimilars Are Highly Similar
to a Reference/Originator
Biosimilars Have No Clinically Meaningful
Differences From a Reference/Originator
Biologic vs Biosimilar
Biosimilars Are NOT Generics!
FDA-approved biosimilars are compared with the FDA-approved biologic
reference/originator product and approved for use in the same indications.
Large and generally
complex molecules
Derived from
living organisms
Carefully monitored to
ensure consistent
quality
Biologic
• Originally licensed product
• Standalone application
• Must contain all data and information
necessary to demonstrate safety and
effectiveness in the treatment of
specified indications
For approval, the structure and function of an approved
biosimilar are compared with the reference/originator,
looking at key characteristics, such as:
Purity Molecular
structure
Bioactivity
Generic
• Relies on data (preclinical/clinical) from an approved small molecule product
• Must demonstrate bioequivalence in terms of concentrations, specifically
over time compared with the reference small molecule
Biosimilar
• Relies on safety and effectiveness data
from the approved reference biologic
• Must demonstrate high similarity and no
clinically meaningful differences in terms
of safety, purity, and potency compared
with the reference biologic
Studies are preformed to show that biosimilars have no
clinically meaningful differences in safety, purity, or potency
compared with the reference/originator product, such as:
Pharmacokinetic
and pharmacodynamic
studies
Immunogenicity
assessment
Additional
clinical studies,
as needed

2. Access the activity, “Biosimilars as Partners in Oncology: Expert
Guidance on Understanding and Incorporating Biosimilar Agents
in Real-World Care,” at PeerView.com/BBG40
Biosimilars: What Are They?
PRACTICE AID
Licensure Pathways for Biologic Products2,3
The Biologics Price Competition and Innovation Act of
2009 (BPCI Act) created an abbreviated licensure pathway
for biological products shown to be biosimilar to or
interchangeable with an FDA-licensed reference product.
The licensure pathway permits a biosimilar biologic product
to be licensed under 351(k) of the Public Health Service
Act (PHS Act) based on less than a full complement of
product-specific preclinical and clinical data.
FDA Definition of a Biosimilar
Biosimilarity means“that the biological product is highly similar to the reference product notwithstanding minor
differences in clinically inactive components; and there are no clinically meaningful differences between the biological
product and the reference product in terms of the safety, purity, and potency.”
FDA approval is granted only for the indications and conditions of use that have been
approved for the reference/originator.
Biosimilars must have
the same MOA, route of
administration, dosage,
and strength as the
reference product
Biosimilars must
meet the rigorous
standards of the
FDA for approval
Biosimilars are
manufactured
in FDA-licensed
facilities
Biosimilars are tracked
through post-market
surveillance to ensure
continued safety
Extrapolation to
other indications
can occur
Abbreviated Licensure Pathway
351(a)
Originator
351(k)
Biosimilar
351(k)(4)
Interchangeable
Biosimilar
351(a)
Non-originator
Biologic
351(a)
Next-generation
"Biobetter"
Product
description
First-to-market
biologic molecule; will
likely be the reference
product
Highly similar to a
reference product;
approved via
biosimilar pathway
A biosimilar that can
be substituted for the
reference without
permission from
prescriber
A product with
another brand
name of an already
approved biologic
Biologic that has been
altered to achieve
improved clinical
outcomes
Type of data
submitted to
the FDA
Standard data
package: efficacy
and safety
Abbreviated
data package for
comparability
More extensive
data package for
comparability, supporting
that the interchangeable
biosimilar anticipated
to produce same
clinical effects for all
the reference product’s
licensed conditions
Standard data
package: efficacy
and safety
Standard data
package: efficacy
and safety
Compared to
originator?
N/A Yes Yes Yes or no
Likely
(standard of care)

3. Access the activity, “Biosimilars as Partners in Oncology: Expert
Guidance on Understanding and Incorporating Biosimilar Agents
in Real-World Care,” at PeerView.com/BBG40
Biosimilars: What Are They?
PRACTICE AID
MOA: mechanism of action; PD: pharmacodynamics; PK: pharmacokinetics.
1. https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars. Accessed March 30, 2020. 2. Lucio SD et al. Am J Health Syst Pharm. 2013;70:2004-2017.
3. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-demonstrating-interchangeability-reference-product-guidance-industry. Accessed
March 30, 2020. 4. Holzmann J et al. Expert Opin Biol Ther. 2016;16:137-142. 5. https://www.fda.gov/files/drugs/published/FDA%E2%80%99s-Overview-of-the-Regulatory-Guidance-for-the-
Development-and-Approval-of-Biosimilar-Products-in-the-US.pdf. Accessed March 30, 2020. 6. Zuniga L, Calvo B. Pharmacoepidemiol Drug Saf. 2010;19:661-669. 7. Casadevall N et al. Expert
Opin Biol Ther. 2013;13;1039-1047.
• A step-wise approach to achieve biosimilarity
• Integration of the foundational, comparative,
analytical, and functional characterization studies
and the supportive nonclinical and clinical studies
• Evaluation of efficacy, safety, and immunogenicity
• Allows for a meaningful prediction of the biological
function and clinical performance
Totality of Evidence4 Extrapolation of Clinical Data
for Multiple Indications5
• The potential exists for a biosimilar product to be
approved for one or more conditions of use for which
the US-licensed reference product is licensed based
on extrapolation of data intended to demonstrate
biosimilarity in one condition of use
• Sufficient scientific justification for extrapolating
data is necessary
• FDA guidance outlines factors that should be
considered when providing scientific justification
for extrapolation
– Requires similar MOA, PK, PD, and immunogenicity
in different patient populations
– Potentially provides substantial savings in drug
development
– Differences in expected toxicities in each condition
of use and patient population
– Differences between conditions of use do not
necessarily preclude extrapolation
• A product is interchangeable when it can be
substituted for its reference product with the
expectation of achieving the same clinical outcome
as the reference product in any patient in a given
clinical setting
• An interchangeable product may be substituted
for the reference product without the intervention
of the healthcare provider who prescribed the
reference product
Interchangeability5 Pharmacovigilance:
Role of the Provider6,7
• Be aware of which biosimilar product is being
prescribed and used
• Prescribe using the proper name or trade name
with suffix
• Contribute to local pharmacovigilance efforts
(registries)
• Monitor long-term safety
• Encourage transparency in drug characterization

4. Access the activity, “Biosimilars as Partners in Oncology: Expert
Guidance on Understanding and Incorporating Biosimilar Agents
in Real-World Care,” at PeerView.com/BBG40
Oncology Biosimilars
PRACTICE AID
FDA-Approved Oncology Biosimilars1
Selected Oncology Biosimilars in Development2-6
APPROVALS APPROVALSAPPROVALS
Bevacizumab Rituximab Trastuzumab
• Adults with NHL
• Adults with CLL
• Rheumatoid arthritis,
granulomatosis with
polyangiitis, and
pemphigus vulgaris
• Metastatic CRC
• Unresectable, locally
advanced, recurrent or
metastatic nonsquamous
NSCLC
• Adults with recurrent
glioblastoma
• Metastatic RCC
• Persistent, recurrent or
metastatic cervical cancer
• Epithelial ovarian,
fallopian tube, or primary
peritoneal cancer
INDICATIONS
Reference Biologic Drug Class Indications Ongoing and Upcoming ClinicalTrials
• HER2-overexpressing
metastatic breast cancer
• HER2-overexpressing
metastatic gastric or
GEJ adenocarcinoma
BCD-021 (preclinical), BEVZ92/MB0 (preclinical),
BI 695502 (completed), CT-P16 (one completed
and one recruiting), HD204 (one completed and
one recruiting), and SB8 (completed)
CRC, lung, and
renal cancer
VEGF inhibitorBevacizumab
ABP 494 (preclinical), STI-001 (preclinical),
CMAB009 (one completed and two recruiting)
CRCEGFR inhibitorCetuximab
ABP 798 (completed), BCD-020 (completed),
DRL_RI (recruiting), MabionCD20 (recruiting),
RTXM83 (completed), and SAIT101
(one completed and one active/not recruiting)
LymphomaCD20 inhibitorRituximab
EG12014 (one completed and one recruiting)
and HD201 (one completed and one
active/not recruiting)
Breast cancerHER2 inhibitorTrastuzumab
• Bevacizumab-awwb
(ABP 215), Sept 2017
• Bevacizumab-bvzr
(PF-06439535), June 2019
• Trastuzumab-dkst
(MYL-1401O), Dec 2017
• Trastuzumab-pkrb
(CT-P6), Dec 2018
• Trastuzumab-dttb
(SB3), Jan 2019
• Trastuzumab-qyyp
(PF-05280014), March 2019
• Trastuzumab-anns
(ABP980), June 2019
• Rituximab-abbs
(CT-P10), Nov 2018
• Rituximab-pvvr
(PF-05280586), July 2019
INDICATIONS
INDICATIONS

5. Access the activity, “Biosimilars as Partners in Oncology: Expert
Guidance on Understanding and Incorporating Biosimilar Agents
in Real-World Care,” at PeerView.com/BBG40
Supportive Care Biosimilars
PRACTICE AID
AML: acute myeloid leukemia; ANC: absolute neutrophil count; BMT: bone marrow transplantation; CKD: chronic kidney disease; CLL: chronic lymphocytic leukemia; CRC: colorectal cancer;
FN: febrile neutropenia; GEJ: gastroesophageal junction; G-CSF: granulocyte colony-stimulating factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; NHL: non–Hodgkin lymphoma;
NSCLC: non–small cell lung cancer; RBC: red blood cell ; RCC: renal cell carcinoma; VEGF: vascular endothelial growth factor.
1. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information. Accessed March 30, 2020. 2. Stevenson JG et al. Ann Pharmacother. 2017;51:590-602. 3. Rugo HS et al. Cancer Treat Rev.
2016;46:73-79. 4. Panesar K. US Pharm. 2016;41:26-29. 5. www.clinicaltrials.gov. March 30, 2020. 6. Busse A, Luftner D. Breast Care (Basel). 2019;14:10-16. 7. Botteri E et al. Eur J Cancer. 2018;89:49-55.
8. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Growth Factors. Version 2.2020. https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf. Accessed March 30, 2020.
FDA-Approved Supportive-Care Biosimilars1
Therapeutic and Preventative Use of Myeloid Growth Factors7,8
• Filgrastim-sndz
(EP6000), March 2015
(first approved biosimilar)
• Filgrastim-aafi
(PF-06881893), July 2018
Therapeutic
• Sepsis syndrome
• ANC <100/μL
• Neutropenia likely to exceed 10 days
• Neutropenia and pneumonia or other infections
• Neutropenia and invasive fungal infection
• Neutropenia and hospitalization with fever
Preventative
• Prior FN
• High likelihood of incidence of FN
• Aged >65 years
Myeloid growth factors used therapeutically
• G-CSF: filgrastim (tbo-filgrastim, filgrastim-sndz,
and filgrastim-aafi)
• GM-CSF: sargramostim
Myeloid growth factors used prophylactically
• G-CSF: filgrastim (tbo-filgrastim, filgrastim-sndz,
and filgrastim-aafi)
• PEGylated G-CSF: pegfilgrastim (pegfilgrastim-
bmez, pegfilgrastim-cbqv, and pegfilgrastim-jmdb)
APPROVALS APPROVALSAPPROVALS
• Pegfilgrastim-jmdb
(MYL-1401H), June 2018
• Pegfilgrastim-cbqv
(APO-Peg), Nov 2018
• Pegfilgrastim-bmez
(LA-EP2006), Nov 2019
• Epoetin alfa-epbx
May 2018
• Decrease of infection (FN) in
pts with nonmyeloid cancer
receiving myelosuppressive
anticancer drugs
• Reduce time to neutrophil
recovery/duration of fever
in AML
• Reduce duration of neutropenia
while undergoing myeloablative
chemotherapy, followed by BMT
• Mobilize autologous hematopoietic
progenitor cells into peripheral
blood for leukapheresis
• Increase survival in hematopoietic
syndrome of acute radiation
syndrome
• Reduce incidence and duration of
sequelae of severe neutropenia in
neutropenic disorders
• Anemia due to the effects of
concomitant myelosuppressive
chemotherapy, and upon
initiation, there are a minimum
of 2 additional months of
planned chemotherapy
• Anemia due to CKD,
independent of dialysis
• Anemia due to zidovudine in
patients with HIV
• Reduction of allogeneic RBC
transfusions in patients
undergoing elective, noncardiac,
nonvascular surgery
• Decrease incidence of
infection (FN) in patients
with nonmyeloid
malignancies receiving
myelosuppressive
anticancer drugs
• Increase survival in
hematopoietic syndrome
of acute radiation
syndrome
Indications
PegfilgrastimFilgrastimEpoetin Alfa
INDICATIONS
INDICATIONS
INDICATIONS