Granulocyte-Colony Stimulating Factor Biosimilars

An Update for Frontline Oncology Practitioners

This educational activity is jointly accredited for nurses and pharmacists and is supported

by an independent educational grant from Pfizer, Inc.

Faculty

Sandra Cuellar, PharmD, BCOP

Clinical Associate Professor, Pharmacy Practice

University of Illinois at Chicago College of Pharmacy

Oncology Resident Director, Ambulatory Pharmacy Services

UI Health

Chicago, IL

Dr. Cuellar is a Clinical Associate Professor in the Department of

Pharmacy Practice at the University of Illinois at Chicago (UIC) College

of Pharmacy. Dr. Cuellar is a Board-Certified Oncology Pharmacist and works as a clinical

oncology pharmacist at UI Health. She serves as the oncology residency program director,

member of the DSMC, and vice-chair of the IRB. She is an invited lecturer, providing numerous

national and international presentations on cardio-oncology, supportive care oncology,

biosimilars, and oncology therapeutics.

Faculty

Kristi Orbaugh, MSN, RN, NP, AOCN

Adult Nurse Practitioner

Community Hospital Oncology Physicians

Indianapolis, IN

Kristi Orbaugh has spent her entire career in the oncology field. She received her

undergraduate degree from Purdue University and her master’s degree from Indiana

University—Purdue University of Indianapolis. She works as a nurse practitioner at

Community Hospital Cancer Center North, which is an affiliate of MD Anderson. She has

published several oncology-related articles. Ms. Orbaugh is passionate about oncology and

enjoys presenting and providing oncology education on regional, national, and international

levels.

Disclosures

Dr. Cuellar has disclosed that she has served as a consultant for Coherus Biosciences and

Pfizer, Inc.

Ms. Orbaugh has disclosed that she has served on the Speaker’s Bureau for Bristol-Myers

Squibb, Coherus Biosciences, Dova, Immunomedics, Lilly, Morphos, Pfizer, Inc. and Rigel.

The clinical reviewer, Megan May, PharmD, BCOP has no actual or potential conflict of interest

in relation to this program.

Susanne Batesko, BSN, RN, Robin Soboti, RPh, and Susan R. Grady, MSN, RN, as well as the

planners, managers, and other individuals, not previously disclosed, who are in a position to

control the content of Postgraduate Healthcare Education (PHE) continuing education activities

hereby state that they have no relevant conflicts of interest and no financial relationships or

relationships to products or devices during the past 12 months to disclose in relation to this

activity. PHE is committed to providing participants with a quality learning experience and to

improve clinical outcomes without promoting the financial interests of a proprietary business.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the

Postgraduate Institute for Medicine and Postgraduate Healthcare Education. Postgraduate

Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical

Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the

American Nurses Credentialing Center (ANCC), to provide continuing education for the

healthcare team.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is

1.25 contact hours. Pharmacotherapy contact hours for Advanced Practice Registered

Nurses will be designated on your certificate.

Pharmacy Accreditation

Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for

Pharmacy Education as a provider of continuing pharmacy education.

UAN: 0430-9999-21-003-H01-P

Credits: 1.25 hour (0.125 CEU)

Type of Activity: Application

Learning Objectives

• Discuss the current data supporting short- and long-acting granulocyte-colony stimulating factor (G-CSF) use in prevention of febrile neutropenia and during the COVID-19 era

• Formulate practical approaches to incorporating G-CSF biosimilars into healthcare system formularies and/or clinical pathways

• Recognize the need for educational interventions that will improve healthcare providers’ understanding of G-CSF biosimilars use in cancer supportive care

G-CSF Biosimilars Overview

G-CSF Biosimilars Overview

• Definition of a biosimilar

• Brief overview of the approval process

• Short- and long-acting G-CSF biosimilars currently available

• Similarities and differences of currently approved biosimilars and originator products

A Bio-What?

Biosimilars

• Biosimilar: a biologic product highly similar to a previously FDA-licensed biologic product that has been previously licensed by the FDA

• Licensed product is referred to as the “reference product”

• Derived from living organisms or living cells

• Larger and much more complex than small molecule medications

• Variability is allowed• No clinically meaningful difference in safety, potency, or purity

Cook JW, et al. Ther Adv Med Oncol. 2019;11:1758835918818335.

Biosimilar Approval Process

• Demonstrate there are no clinically meaningful differences between reference product and biosimilar

• Detailed analytical and structural testing• FDA reviews evidence from comparative analytical, nonclinical, clinical

pharmacology, and clinical studies in a stepwise approach

• Studies compare purity, potency, and efficacy to the reference product

• Pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity studies

• Human studies initially conducted in healthy subjects to reduce PK/PD variability

Waller CF, Friganovic A. Future Oncol. 2020;16(25):1931-1939.;Lyman GH, et al. J Clin Oncol. 2018;36(12):1260-1265.

Available G-CSF Biosimilars

Short-acting FDA Approved

Zarzxio (filgrastim-sndz) March 2015

Nivestym (filgrastim-aafi) July 2018

Pegylated, long-acting

Fulphila (pegfilgrastim-jmdb) June 2018

Udenyca (pegfilgrastim-cbqv) November 2018

Ziextenzo (pegfilgrastim-bmez) November 2019

Nyvepria (pegfilgrastim-apgf) June 2020

European Medicines Agency has approved 8 filgrastim and 5 pegfilgrastim biosimilars

Frazer MB, et al. J Oncol Pharm Pract. 2020;26(3 suppl):3-10.

Similarities and Differences

• Tbo-filgrastim (Granix) is not considered a biosimilar• Approved as an original biologic prior to development of FDA biosimilar

process

• Similar to the originator product, but a more limited indication

• ASCO and NCCN guidelines

• Some G-CSF biosimilars (i.e., filgrastim-aafi, filgrastim-sndz) have the same indications as the originator product

• Other biosimilars have more limited indications

• Filgrastim (Neupogen) has the only indication for acute radiation syndrome

Wicherska-Pawlowska K, et al. J Clin Apher. 2020;35(1):4-8.; NCCN Clinical Practice Guidelines in Oncology. Hematopoietic Growth Factors. Version 2.2020– January

27,2020.; https://www.asco.org/practice-policy/policy-issues-statements/asco-in-action/media-issue-brief-biosimilars

Discussion

G-CSF Reference Products and Biosimilars in Supportive Care

Supportive Care with Biosimilars

• Febrile neutropenia prevention

• Neutropenia treatment

• Mobilization for hematopoietic stem cell transplantation

• Neutrophil recovery post-hematopoietic stem cell transplantation

• Coronavirus disease (COVID)-19

Neutropenia Prevention and Treatment

• Neutropenia is a significant threat for patients with cancer• Affects approximately 50% of patients undergoing myelosuppressive

chemotherapy

• Febrile neutropenia prevention• NCCN recommends G-CSF for all patients receiving chemotherapy

regimens deemed high risk (>20%)

• Goal is to• Shorten length of neutropenia

• Decrease hospitalization risk

• Decrease length of hospitalization

Smith TJ, et al. J Clin Oncol. 2015;33(28):3199-3212.; NCCN Clinical Practice Guidelines in Oncology.

Hematopoietic Growth Factors. Version 2.2020– January 27,2020.

Mobilization and Neutrophil Recovery

• G-CSF originators and biosimilars can be used for:• Stem cell mobilization enhancement for HSCT

• Neutrophil recovery post-HSCT

• Post-treatment prophylaxis

• Reduce number of days required for neutrophil engraftment post-treatment

• Reduce antibiotic therapy and hospitalization length

Pahnke S, et al. Bone Marrow Transplant. 2019;54(6):858-866.

HSCT=hematopoietic stem cell transplantation

Impact of COVID-19 Pandemic

• NCCN extended recommendation for prophylactic G-CSF • Intermediate risk for FN (10% to 20%).

• May also be appropriate in patients receiving low-risk regimens (<10%)

• Multiple comorbidities or age puts them at higher FN risk

https://www.nccn.org/covid-19/pdf/HGF_COVID-19.pdf

Caution with COVID-19

• Consider discontinuing/avoiding G-CSF use in patients with• Respiratory symptoms

• Respiratory infection

• Confirmed or suspected COVID-19

• Decrease the risk of increased pulmonary inflammation

• Decrease hypothetical risk of increased inflammatory cytokines• Associated with possible adverse outcomes

https://www.nccn.org/covid-19/pdf/HGF_COVID-19.pdf

Discussion

Biosimilar Integration:Issues & Challenges

Biologics are the cornerstone of cancer treatment

Biologics are expensive and costs are increasing progressively

Biosimilars increase market competition without compromising efficacy or safety

Disrupting the Pharmaceutical Biologic Ecosystem

Cost Savings: Real World

University Hospitals Health System

in Ohio•$>450,000 annualized cost avoidance

implementation of biosimilar filgrastim-sndz

Kalispell Regional Medical Center in

Montana•Biosimilar peg-filgrastim-cbqv saved

medical center $350,000 (12 months)

Easley H, Klotz M. ASHP Midyear 2020 Poster Presentation. December 8, 2020.

Kar I., et al. ASHP Midyear 2020 Poster Presentation. December 7, 2020.

Variables to Successful Biosimilar Integration into Health Care System

Manufacturing &

Development of

Biosimilar Products

Biosimilar

Integration into

Oncology

Practice

Scientific Community:

Data Evaluation,

Guidelines, Position

Statements

Pharmacovigilance

Efficacy & Safety

Healthcare

Professional & Patient

Acceptance

FDA Regulatory

Pathway

Degree of

Pharmacoeconomic

Benefit

Payer & Institutional

Acceptance

Dolan C. Am J Manag Care. 2018;24(suppl 11):S237-S243

• Understanding biosimilar development program• FDA approval based on totality of evidence

• Clinical data• Switching studies

• Clinical trial design• Data in curative versus non-curative setting

• Endpoints (e.g., response rates, progression free survival)

• Extrapolation indications

• Safety• Immunogenicity

Biosimilar Education: Efficacy & Safety

Cohen, et al. conducted a survey from November 2015 to January 2016 among specialty physicians

Objective was to assess current physician awareness, knowledge, and perceptions regarding biosimilars

19 question survey created by Biosimilars Forum

Administered by an independent 3rd party

Cohen H, et al. Adv Ther. 2017;33(12):2160-2172..

Provider Awareness

Challenges: Provider Awareness

Which of the following statements are true when the

FDA approves a biosimilar?Medical-

Oncologists

Hematologist-

Oncologists

The biosimilar will have equivalent efficacy

as its originator brand counterpart.67.5% 69.0%

The biosimilar will be at least as safe as

its originator brand counterpart.66.5% 62.5%

A pharmacist will be allowed to substitute

a biosimilar for the originator brand

counterpart without asking the prescriber. 18.5% 17.5%

The biosimilar will always be approved for

all of the indications of use of the

originator brand counterpart. 28.5% 37.0%

Cohen H et al. Adv Ther. 2017;33(12):2160-2172.

Manufacturing &

Development of

Biosimilar Products

Biosimilar

Integration into

Oncology

Practice

Scientific Community:

Data Evaluation,

Guidelines, Position

Statements

Pharmacovigilance

Efficacy & Safety

Healthcare

Professional & Patient

Acceptance

FDA Regulatory

Pathway

Degree of

Pharmacoeconomic

Benefit

Payer & Institutional

Acceptance

Dolan C. Am J Manag Care. 2018;24(suppl 11):S237-S243

Variables to Successful Biosimilar Integration into Health Care System

Calculating Pharmacoeconomic Benefit

X

AC +/- %

7 8 9

4

1

5 6

2 3

0 .

Cost & Revenue (Inpatient/Outpatient)

Payer Mix

Group Purchasing Organizations

340B

Rebate Arrangements

Patient Out-of-Pocket Costs

Biosimilar Reimbursement

Reference Product

vs.

Biosimilar

Challenges with Financial Analysis

• G-CSF

• PegfilgrastimMultiple

Biosimilars

• Medicare, Medicaid

• Commercial InsurancesMultiple Payer

Policies

• Onpro DeviceProduct Administration

Differences

Biosimilar Reference

biologic

Price competition

Purchase price Rebate

Payment rates &utilization management

Providers Insurers

Prescribing

decisions

Patients

Cost

sharing Premiums

Manufacturers

Onpro Pegfilgrastim vs. Biosimilar Pegfilgrastim

Increased convenience

Reduced drug administration burden on

healthcare system

Device failures

Higher cost

• Reported device failure rate 1% to 10%

• May result in higher costs

• Patient preference • Insurance coverage

• Medicare • Medicaid• Commercial

McBride A, et al. J Med Econ. 2020;23(1):28-36.;

Bittner B, et al. BioDrugs. 2018;32(5):425-440.

Pivotal Initial Steps: Biosimilar Integration

HCP Biosimilar

Acceptance

Pharmaco-

economic Benefit

Formulary

Preparation

Discussion

Best Practices for Biosimilar Integration

• Evaluate safety, efficacy, and economic value of medication use in an institution

• Identify institution physician/pharmacy champion • Determine current biologic utilization

• Forecast potential economic benefit of biosimilars

• Resource for scientific review of biosimilars

• Biosimilar implementation strategy

• Resources • GPO may have side-by-side comparisons of biosimilars

• Facts and Comparisons Formulary service

• Drug information monograph service

P&T Committee: Gateway to Biosimilar Adoption

P&T=Pharmacy & Therapeutics

GPO=Group Purchasing Organization

Other Key Considerations: Formulary

• Medication availability

• History shortages & recalls

• Handling practices

• Supply chain security

• Patient assistance programs

Manufacturer Considerations

Griffith N, et al. Hosp Pharm. 2014;49(9)813-825.

• Packaging & labeling

• Product storage & administration

• Interchangeability

• Indications

• IT support

Hospital Considerations

• Members of departments involved with transition from reference product to biosimilar

• Map out transition process and launch date

• Determine the operational impact (inpatient/outpatient) of biosimilar adoption

Biosimilar Task Force

Griffith N, et al. Hosp Pharm. 2014;49(9)813-825. Tyler LS et al. Am J Health Syst Pharm 2008;13:1272-1283.

• Create biosimilar policy & procedures

• Patient consent

• EMR implementation

• Financial authorization for preferred biosimilar• Process for outpatient denial of biosimilar

• Transition decision• Naive patients versus switching patients

• Education • Nurses, pharmacists, physicians, patients

• Pharmacy inventory & storage

Biosimilar Task Force:Operational Impact

Griffith N, et al. Hosp Pharm. 2014;49(9)813-825.;Tyler LS et al. Am J Health Syst Pharm. 2008;13:1272-1283.

EMR=electronic medical record

• Be prepared to carry different products

• Be prepared to re-evaluate economic evaluation• Policies change

• Biosimilar payer restrictions

• Monitoring• Determine who will monitor biosimilar integration

• Establish metrics

• Establish timelines for follow-up

Other Factors

Pegfilgrastim Biosimilar Implementation Timeline

Month Preparing for Biosimilar Use Formulary Evaluation and Full Transition

Oct 2018 • Assess scope of impact

• Identify affected ordering tools

N/A

Nov 2018 • Determine availability and

communicate use to wholesaler

• Prepare formulary monograph

Dec 2018 • Convene stakeholders

• Update charts and references

• Configure medication record

• Procure product

• Identify evidence gaps that may preclude full biosimilar

transition

• Identify patients enrolled in PAP for reference product

• Determine financial impact

Jan 2019 • Payer policy requiring biosimilar

goes into effect; product and

medication record available for use

• P&T committee review and formulary addition of a

biosimilar product, TBD based on pricing opportunities

• Manage inventory (weekly counts until supply is

depleted)

• Update consent forms to include nonproprietary names

or equivalent

Villanueva M, et al. Am J Health Syst Pharm. 2021;78(3)249-260. MD Anderson Cancer Center

Pegfilgrastim Biosimilar Implementation Timeline

Month Preparing for Biosimilar

Drug UseFormulary Evaluation and Full Transition

Feb 2019 N/A • Explore pricing opportunities and determine formulary product

• Configure biosimilar medication orderable record and swap for

reference in standard of care treatment protocols

Mar 2019 N/A • Set go-live date based on supplies and timeline for treatment

protocol updates

• Validate biosimilar medication record swaps

• Incorporate into workflows for financial clearance and prior

authorization

Apr 2019 N/A • Communicate formulary change

• Formulary transition go-live (newly applied treatment plans)

May 2019 N/A • Transition current patients

• Formulary deletion of reference product once supply is depleted,

protocol amendments are approved, and active treatment plans

have been updated

Villanueva M, et al. Am J Health Syst Pharm. 2021;78(3)249-260. MD Anderson Cancer Center

Key Considerations: MD Anderson Experience

• Collaboration of pharmacy and pharmacy informatics personnel

• Implementing optimal ordering tools

• Implications on research protocols (e.g., consenting process)

• Protocol amendments

• Stocking the reference and biosimilar product(s) during transition period and potentially beyond

• Processes to oversee inventory and minimize error risk

Villanueva M, et al. Am J Health Syst Pharm. 2021;78(3)249-260.

• Opportunity for health systems to improve financial health

• Key preliminary steps include determining financial impact and provider acceptance

• P&T formulary preparation and approval are vital to biosimilar adoption

• All impacted stakeholders must convene and map out mechanics to operationalize process

• Inpatient and outpatient settings

Summary

Questions & Answers

Thank you!