midwinter meeting february 29, 2020...de ridder l, et al. j pediatr gastroenterol nutr. 2015...

Midwinter MeetingFebruary 29, 2020

Biosimilars: Same, Same… but Different

Whitney Mortensen, PharmD, MBA, BCPSDrug Information Services Manager

Intermountain Healthcare

Disclosure

No conflicts of interest to disclose.

Off-label uses of medications will be discussed.

Learning Objectives

At the conclusion of this activity, pharmacists should be able to successfully:

1. Describe the differences between small-molecule drugs and biologics

2. Identify positions taken by professional organizations relating to the use of biosimilars

3. Evaluate the evidence on switching a patient from a biologic to a biosimilar

4. Review the current landscape of biologics and list biosimilars in the approval pipeline

5. Compare and contrast biologics and biosimilars in terms of cost and patient assistance options

Learning Objectives

At the conclusion of this activity, pharmacy technicians should be able to successfully:

1. Describe the differences between small-molecule drugs and biologics

2. List professional organizations that have taken a stance on the use of biosimilars

3. Review the current landscape of biologics and list biosimilars in the approval pipeline

4. Compare and contrast biologics and biosimilars in terms of cost and patient assistance options

Basics of Biologic and Biosimilar Drugs

Key DifferencesCharacteristic Generics BiosimilarsChemically identical to originator

Approval on bioequivalence not clinical data

Same nonproprietary name as originator

Therapeutically equivalent/interchangeable at time of approval

Clear and consistent state laws around interchangeability

Familiar to health care providers and general public

Value clearly defined and understood

Kozlowski S, et al. N Engl J Med. 2011;365(5):385-388.Lucio S. Biosimilars & Biologics, 1st ed. 2018.

Small Molecules vs Biologic Drugs

Small-molecule drugs• Simple structures

• Easily defined and replicated

• Chemical-based

Biologics• Large, complex structures

• Difficult to replicate (variability between batches)

• Protein-based

Kozlowski S, et al. N Engl J Med. 2011;365(5):385-388.Lucio S. Biosimilars & Biologics, 1st ed. 2018.

Small Molecules vs Biologic Drugs

Kozlowski S, et al. N Engl J Med. 2011;365(5):385-388.

Approval Pathways

Peterson J, et al. J Manag Care Spec Pharm. 2017 Dec;23(12):1255-1259.Lucio S. Biosimilars & Biologics, 1st ed. 2018.

• Highly similar to reference product

• Minor differences in the inactive components

• No clinically meaningful differences in safety, purity, or potency

• Approved based on a totality-of-the-evidence approach

Biosimilars Approval

FDA approval

Analytical studies

PK/PD studies

Animal studies

Immuno‐genicitystudies

Clinical trials

FDA = Food and Drug Administration; PD = pharmacodynamic; PK = pharmacokinetic

Biosimilar Development, Review, and Approval. U.S. Food & Drug Administration. 2017.

Biologic vs Biosimilar Approvals

Lucio S. Biosimilars & Biologics, 1st ed. 2018.

Clinical trials

Clinical pharmacology

Nonclinical

Lead selection

Clinical trials

Clinical pharmacology

Nonclinical

Analytical (similarity)

Biologics Biosimilars

Nonproprietary names contain an FDA-designated suffix• Biologics and biosimilars share a core name

• Core name and suffix connected with a hyphen

• Suffix used to distinguish between products

FDA Naming Conventions

InFLIXimab - abda

Bevacizumab - awwb

Nonproprietary Naming of Biological Products: Guidance for Industry. U.S Food & Drug Administration. 2019.

• Interchangeability distinction unique to the United States

• Interchangeable biosimilars may be substituted without a prescriber’s order (eg, by a pharmacist)

• Purple Book lists biologics, biosimilars, and interchangeability

Biosimilars and Interchangeability

Lucio S. Biosimilars & Biologics, 1st ed. 2018.Franklin J. Biosimilar and Interchangeable Products. 2018. Purple Book. U.S Food & Drug Administration. 2019.

• Pharmacists may substitute an interchangeable biologic product if:• Patient requests or consents to the interchange• Patient is notified of interchange and counseled • Interchange is documented• Prescriber is notified within 5 business days• Prescription is not designated “dispense as written”

Interchangeability –Utah Pharmacy Practice Act

Utah Pharmacy Practice Act 58‐17b‐605.5

Which of the following statements about biosimilars are TRUE (select all that apply)?A. Biosimilars follow the same approval pathway as generics

B. Biosimilars are highly similar to the reference biologic drug with no clinically meaningful differences in safety, purity, or potency

C. Biosimilars are large, complex, protein-based structures

D. Biosimilars are like small-molecule generic drugs and can be substituted without contacting the prescriber before or after the substitution

Audience Question –Pharmacists and Technicians

Global Experiences and Clinical Considerations

European Union first approved a biosimilar in 2006• Currently more than 35 biosimilars on the market

• Safe and effective• Lower cost• Improved access

Other countries with approved biosimilars• Australia (2010), Canada (2009), Japan (2009), South Korea (2012), United States (2015)

Global Approach


Professional Organizations –Inflammatory Conditions

Lichtenstein GR, et al. Am J Gastroenterol. 2018 Apr;113(4):481-517.Danese S, et al. J Crohns Colitis. 2017 Jan;11(1):26-34.NRAS position paper on biosimilar medicines – revised 2017. National Rheumatoid Arthritis Society. 2017.

Organization RecommendationsACG 2018 • Adalimumab and inFLIXimab biosimilar products are effective/safe for induction and

maintenance therapy in moderate-to-severe Crohn’s disease• Insufficient data to support multiple switching in stable Crohn’s disease patients

ECCO 2017 • Acceptable to switch from the originator to a biosimilar in patients with IBD • Evidence lacking for multiple switching in IBD patients • Switching from the originator to a biosimilar should done following appropriate discussion

between physicians, nurses, pharmacists, and patientsNRAS 2017 • New patients may be started on a biosimilar with approval of prescriber and patient consent

• Substitution of a biosimilar product should only occur under direct supervision and consent of prescriber and with patient agreement

ACG = American College of Gastroenterology; ECCO = European Crohn’s and Colitis Organization; IBD = inflammatory bowel disease; NRAS = National Rheumatoid Arthritis Society

Professional Organizations –Inflammatory Conditions

Organization RecommendationsACR 2018 • Prescriber should decide if appropriate to substitute a biosimilar for a reference product or if

appropriate to switch between biosimilars • Switching stable patients to a different medication for cost saving reasons should only occur

with prescriber consent• Biosimilar indications should not be routinely granted based solely on the reference product• Off-label use of a biosimilar may be appropriate

ACR 2017 • Support rules requiring robust switching studies to determine if alternating between products impacts safety or efficacy

EULAR 2016 • Biosimilar DMARDs have similar efficacy and safety as reference DMARDs and should be preferred if less expensive

ESPGHAN 2015

• Recognize that biosimilars are highly similar to reference product • Little data on use IBD; advocate for pediatric trials and post-marketing surveillance

ACR = American College of Rheumatology; DMARD = disease-modifying antirheumatic drug; ESPGHAN = European Society for Paediatric Gastroenterology Hepatology and Nutrition; EULAR = European League Against Rheumatism; IBD = inflammatory bowel disease

Committee on Rheumatologic Care. American College of Rheumatology Position Statement: Biosimilars. American College of Rheumatology. 2018.Lakhanpal S. American College of Rheumatology Responds to FDA Draft Guidance on Biosimilar Interchangeability. American College of Rheumatology. 2017. Smolen JS, et al. Ann Rheum Dis. 2017 Jun;76(6):960-977.De Ridder L, et al. J Pediatr Gastroenterol Nutr. 2015 Oct;61(4):503-8.

Professional Organizations - Oncology

Hematopoietic Growth Factors, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network. 2020.Pahnke S, et al. Bone Marrow Transplant. 2018 Oct 3.Smith TJ, et al. J Clin Oncol. 2015;33:3199-212.Duong HK, et al. Biol Blood Marrow Transplant. 2014;20:1262-73.Aapro MS, et al. European J Cancer. 2011;47:8-32.

Organization RecommendationsNCCN 2018 • Filgrastim biosimilars and pegfilgrastim biosimilars are appropriate substitutes for the

reference products• Filgrastim-sndz, filgrastim-aafi• Pegfilgrastim-jmdb, pegfilgrastim-abqv, pegfilgrastim-bmez• Epoetin alfa-epbx

• Tbo-filgrastim consistently listed as an alternate option along with filgrastim and biosimilarsWMDA 2018 • Stem Cell Donor Registries may use biosimilar filgrastim for peripheral blood progenitor cell

mobilization in healthy donorsASCO 2015 • Biosimilars can be used for the prevention of treatment-related febrile neutropeniaASBMT 2014 • Large studies needed prior to recommending biosimilars during stem cell mobilizationEORTC 2011 • Biosimilars are an option for treatmentACSO = American Clinical Society of Oncology; ASBMT = American Society for Blood and Marrow Transplantation; EORTC = European Organization for Research and Treatment of Cancer; NCCN = National Comprehensive Cancer Network; WMDA = World Marrow Donor Association

True or false: Professional organizations have made recommendations on the use of biosimilars in oncologic and inflammatory conditions.

A. True

B. False

Audience Question – Technicians

True or false: Professional organizations are generally supportive of multiple switches between the reference biologic drug and biosimilars.

A. True

B. False

Audience Question – Pharmacists

Immunogenic adverse effects are a risk of all biologic drugs• Various factors increase risk of developing anti-drug antibodies

• Development of antibodies does not necessarily impact efficacy or safety

Safety Considerations

Intermittent administration

Long‐term treatment

Subcutaneous route Lower doses Immuno‐

competent


Data support switching from inFLIXimab (Remicade®) to a biosimilar• Similar clinical response rates with no significant differences in adverse effects

or immunogenicity

• Dose adjustments may be needed upon switch

Inflammatory Conditions

Choe JY, et al. Ann Rheum Dis. 2017 Jan;76(1):58-64. Smolen JS, et al. Rheumatology (Oxford). 2017 Oct 1;56(10):1771-1779.Smolen JS, et al. Ann Rheum Dis. 2018 Feb;77(2):234-240. Yoo DH, et al. Ann Rheum Dis. 2013;72(10):1613-20.Yoo DH, et al. Arthritis Research & Therapy. 2016;18:82. Yoo DH, et al. Ann Rheum Dis. 2017 Feb;76(2):355-363.

Notable Immunogenicity Clinical TrialsStudy Design/

population Interventions Results

Choe 2017Smolen 2017Smolen 2018

RCT, DB, MC(N = 584)

Adults with RA for at least 6 months

IFX-abda or IFX 3 mg/kg on weeks 0, 2, 6, 14, 22, 30, 38, 46, and 54, with extension study to week 78

At week 54, IFX-abda found equivalent to IFX in ACR20 response rates (65.3% vs 69.2%, 95% CI -12% to 5.86%); similar results seen with ACR50 and ACR70 response rates

At week 78, patients switched from IFX to IFX-abda had similar, slightly lower, ACR20 response rates as those who stayed on therapy (IFX/IFX-abda = 63.5%, IFX/IFX = 68.8%, IFX-abda/IFX-abda = 68.3%)*

No significant differences in adverse effects or immunogenicity between groups

*Post-hoc analysis suggests that this lower response rate was due to the subgroup of patients who were not dose-adjusted after switching from IFXACR = American College of Rheumatology; DB = double blind; IFX = inFLIXimab; IFX-abda = inFLIXimab-abda (Renflexis™); MC = multicenter; RA = rheumatoid arthritis; RCT = randomized controlled trial

Choe JY, et al. Ann Rheum Dis. 2017 Jan;76(1):58‐64. Smolen JS, et al. Rheumatology (Oxford). 2017 Oct 1;56(10):1771‐1779.Smolen JS, et al. Ann Rheum Dis. 2018 Feb;77(2):234‐240.

Data primarily from crossover trials in healthy volunteers• Pegfilgrastim (Neulasta®) and biosimilars

• No difference in maximum ANC or ANC AUC0-t

• Filgrastim (Neupogen®) and biosimilars• No difference in maximum ANC or ANC AUC0-t, xt

Oncologic Indications

Waller CF, et al. J Cancer Res Clin Oncol. 2018 Jun;144(6):1087-1095.Sorgel F, et al. BioDrugs. 2015;29:123-31.Waller CF, et al. Ann Hematol. 2010;89:927–33.Waller CF, et al. Ann Hematol. 2010;89:971–8.Lubenau H, et al. BioDrugs. 2009;23:43-51.Lubenau H, et al. Int J Clin Pharmacol Ther. 2009;47:275-82.

ANC = absolute neutrophil; AUC = area under the curve

Which of the following statements about switching therapy from inFLIXimab(Remicade®) to inFLIXimab-abda (Renflexis®) are TRUE (select all that apply)?

A. Patients switched from inFLIXimab (Remicade®) to inFLIXimab-abda (Renflexis®) had similar clinical response rates as patients who did not switch products

B. Risk of immunogenicity is increased with inFLIXimab-abda (Renflexis®) as compared with inFLIXimab (Remicade®)

C. Dose adjustments are not required after switching products

Audience Question – Pharmacists

Biosimilar Pipeline and Lessons Learned

Current Biosimilars in the United States

Lucio S. Biosimilars & Biologics, 1st ed. 2018. Purple Book. U.S Food & Drug Administration. 2019.Lexicomp. Wolters Kluwer Health. 2020.

Reference product Biosimilar

Bevacizumab (Avastin®) Bevacizumab-awwb (Mvasi™)Bevacizumab-bvzr (Zirabev™)

Filgrastim (Neupogen®)Tbo-filgrastim (Granix®)a

Filgrastim-aafi (Nivestym™)Filgrastim-sndz (Zarxio®)

InFLIXimab (Remicade®) InFLIXimab-abda (Renflexis®)InFLIXimab-dyyb (Inflectra®)

Pegfilgrastim (Neulasta®)Pegfilgrastim-bmez (Ziextenzo™)Pegfilgrastim-cbqv (Udenyca®)Pegfilgrastim-jmdb (Fulphila®)

RiTUXimab (Rituxan®) RiTUXimab-abbs (Truxima®)RiTUXimab-pvvr (Ruxience®)

Trastuzumab (Herceptin®) Trastuzumab-anns (Kanjinti™)Trastuzumab-dkst (Ogivri™)

aTbo-filgrastim (Granix®) is not a true biosimilar

Upcoming Biosimilar Opportunities

Bevacizumab (Avastin®)Etanercept (Enbrel®)

Trastuzumab (Herceptin®)RiTUXimab (Rituxan®) Collagenase (Xiaflex®)

Laronidase (Aldurazye®)Ranibizumab (Lucentis®)

Basiliximab (Simulect®)Natalizumab (Tysabri®)

Panitumumab (Vectibix®)

AbobotulinumtoxinA (Dysport®) Vedolizumab (Entyvio®)Abatacept (Orencia®)Eculizumab (Soliris®)

Adalimumab (Humira®)Alglucosidase alfa (Lumizyme®)

Ustekinumab (Stelara®)

Tocilizumab (Actemra®)Parathyroid hormone (Natpara®)

Romiplostime (NPLATE®)Sipuleucel-T (Provenge®)

Spend estimations based on IQVIA data; IQVIA. 2019.IPD Analytics. IPD Analytics, LLC. 2020. Slide used with permission from Casey Koch, PharmD, BCACP

Disease-specific considerations• Expected length of therapy

• Route of administration

• Multiple indications

Product-specific considerations• Administration device

• Manufacturer provided resources

• Medication supply levels

Key Pipeline Considerations

Slide used with permission from Casey Koch, PharmD, BCACP

• Key patents expired in July 2018 and November 2019 which allowed rituximab biosimilars to come to market • RiTUXimab (Rituxan®) lost exclusivity for oncologic indications only

• Patent protecting granulomatosis polyangiitis and microscopic polyangiitis indications expires May 2020

• Additional patents set to expire in May 2020 and June 2025 protect the rheumatoid arthritis (RA) indication• Even if biosimilar shows efficacy in treating RA, patents prevent a labeled indication• Depending on outcome of ongoing litigation, could see biosimilars indicated for RA as early as

May 2020 or not until June 2025

Patent Implications

IPD Analytics. IPD Analytics, LLC. 2020.

In what year is an adalimumab (Humira®) biosimilar expected to launch in the United States?

A. 2020

B. 2021

C. 2022

D. 2023


Four Key Areas of Focus

FDA – Biosimilar Action Plan (BAP)


1. Improving the efficiency of the biosimilar and interchangeable product development and approval process

2. Maximizing scientific and regulatory clarity for the biosimilar product development community

3. Developing effective communications to improve understanding of biosimilars

4. Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay competition

Biosimilars Action Plan: Balancing Innovation and Competition. U.S. Food & Drug Administration. 2018.

• Developing application review templates for 351(k) Biologics License Applications (BLAs)

• Developing an index of critical quality attributes for use in comparing proposed biosimilars to certain reference products• Increase transparency into how the FDA evaluates comparative analytical studies performed to

support biosimilarity

• Develop and validate pharmacodynamic biomarkers and in silico modeling to evaluate relationships using existing clinical data• Improved efficiency in product creation and reduction in necessary clinical trial size



1. Improving the efficiency of the biosimilar and interchangeable product development and approval process


• Attempting to increase predictability for sponsors

• Increase global partnerships • Harmonize requirements and share regulatory experience• Acceptance of non-U.S. comparator products and real-world data to support regulatory

decision making• Increased efforts to gather data from FDA Adverse Event Reporting System and Sentinel• Partner with private insurers and Centers for Medicare and Medicaid Services



2. Maximizing scientific and regulatory clarity for the biosimilar product development community


• Targeted and unbiased information• www.fda.gov/biosimilars

• Collaborative care• Involve the patient• Importance of counseling



3. Developing effective communications to improve understanding of biosimilars

Biosimilars Action Plan: Balancing Innovation and Competition. U.S. Food & Drug Administration. 2018. Biosimilars. U.S. Food & Drug Administration. 2018.

Negative placebo effect• Patients exhibit negative symptoms because they were told they could experience

those symptoms

• Biosimilar nocebo effect• Patients told they are changing to a biosimilar• How to account for effect in real-world studies

Value of Effective Communication• Counseling patients helps counter the nocebo effect

• Patients must have ample opportunity to ask questions

The Nocebo Effect

Biosimilars Action Plan: Balancing Innovation and Competition. U.S. Food & Drug Administration. 2018.Jørgensen TS, et al. Arthritis Rheumatol. 2017; 69 (suppl 10).


• Reference product drug cost is $6000 per infusion

• Biosimilar product drug cost is $4200 per infusion

• Both covered on the medical benefit with coinsurance of 20%

• If the patient receives infusion of reference product, the member would be responsible for 20% of $6000, or $1200

• If the patient receives infusion of biosimilar product, the member would be responsible for 20% of $4200, or $840

Cost to Patients – Example


Major concern of patients and providers

• Many patients have high deductibles, high maximum out of pocket expense level

• Patient assistance can lower the cost of medication for the patient• Reduces price sensitivity for

the consumer• Has potential negative effects on

cost control

Patient Assistance Programs


Janssen Prescription Assistance. Johnson & Johnson Health Care Systems Inc. 2019.The Merck Access Program. Merck Sharp & Dohme Corp. 2019.Pfizer Encompass. Pfizer Inc. 2018.

InFLIXimab(Remicade®)• Pay $5 per infusion• Maximum $20,000 per calendar year

• No income requirements

InFLIXimab‐abda(Renflexis®)• Pay $5 per infusion• Maximum $20,000 per calendar year


InFLIXimab‐dyyb(Inflectra®)• Pay $0 per infusion• Maximum $20,000 per calendar year


• Reference product drug cost is $6000 per infusion

• Biosimilar product drug cost is $4200 per infusion

• Both covered on the medical benefit with coinsurance of 20%

• If the patient receives infusion of reference product, the member would be responsible for 20% of $6000, or $1200 $5

• If the patient receives infusion of biosimilar product, the member would be responsible for 20% of $4200, or $840 $5

Cost to Patients – Example


True or false: Biosimilar manufacturers typically offer a copay assistance program similar to that of the reference product.

A. True

B. False

Audience Question – Technicians

• Decrease competition blocking

• Limit spread of misinformation

• Promote importance of market competition on pricing



4. Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay competition


Citizen Petition issued by Pfizer – August 2018 • Alleged dissemination of false or misleading information about the safety or efficacy

of biosimilars

• Pushed for FDA to issue guidance on education and communication for biosimilars

Spread of Misinformation

Regulations.gov. Citizen petition from Pfizer Inc. 2018.


$400

$500

$600

$700

$800

$900

$1,000

2015 2016 2017 2018 2019 2020

InFLIXimab ASP Per Vial

Remicade Combined Inflectra/Renflexis Inflectra Renflexis

InFLIXimab-dyyb(Inflectra®) launch

InFLIXimab-abda(Renflexis®) launch


Purple: inFLIXimab (Remicade®)Orange: combined biosimilars

Green: inFLIXimab-dyyb (Inflectra®)Yellow: inFLIXimab-abda (Renflexis®)

ASP = average sales price

What has been the effect on price when multiple biosimilar medications come to market?

A. Reference and biosimilar product costs have increased over time

B. Reference product costs have increased, while biosimilar product costs have decreased

C. Reference product costs have become the same as biosimilar product costs in order to compete

D. Reference and biosimilar product costs have decreased over time


• Biosimilars are highly similar to the reference biologic drug (no clinically meaningful differences)

• Use of biosimilars is generally supported by published literature and guidelines

• Many biosimilars in the pipeline

• Costs decrease as more biosimilars come to market

• Increased education and communication needed

Summary

Regulations.gov. Citizen petition from Pfizer Inc. 2018.


Biosimilars: Same, Same… but Different

Whitney Mortensen, PharmD, MBA, BCPSDrug Information Services Manager

Intermountain Healthcare

• Kozlowski S, Woodcock J, Midthun K, Sherman RB. Developing the nation’s biosimilars program. N Engl J Med. 2011;365(5):385-388.

• Lucio S. Biosimilars & Biologics: Implementation and Monitoring in a Healthcare Setting. 1st ed. Bethesda (MD): American Society of Health-System Pharmacists; 2018. 180 p.

• Peterson J, Budlong H, Affeldt T, et al. Biosimilar products in the modern US health care and regulatory landscape. J Manag Care Spec Pharm. 2017 Dec;23(12):1255-1259

• U.S. Food & Drug Administration [Internet]. Silver Springs (MD): United States Food and Drug Administration; 2019. Biosimilar Development, Review, and Approval; 2017 Oct 20 [cited 2019 Aug 1]. Available from: https://www.fda.gov/drugs/biosimilars/biosimilar-development-review-and-approval.

• U.S. Food & Drug Administration [Internet]. Silver Springs (MD): United States Food and Drug Administration; 2019. Nonproprietary Naming of Biological Products: Update Guidance for Industry; 2019 Mar 15 [cited 2019 Aug 1]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/nonproprietary-naming-biological-products-update-guidance-industry.

• Franklin J. Biosimilar and interchangeable products: the U.S. FDA Perspective [Internet]. Silver Springs (MD): United States Food and Drug Administration; 2018 [cited 2019 Aug 1]. Available from: https://www.fda.gov/media/112818/download

References

• U.S. Food & Drug Administration [Internet]. Silver Springs (MD): United States Food and Drug Administration; 2019. Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations; 2019 Jul 2 [cited 2020 Jan 20]. Available from: https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/purple-book-lists-licensed-biological-products-reference-product-exclusivity-and-biosimilarity-or.

• Utah Pharmacy Practice Act 58-17b-605.5.• Lichtenstein GR, Hanauer SB, Sandborn WJ, et al. American College of Gastroenterology

guidelines on the management of Crohn’s disease in adults. Am J Gastroenterol. 2018 Apr;113(4):481-517.

• Danese S, Fiorino G, Raine T, et al. ECCO position statement on the use of biosimilars for inflammatory bowel disease – an update. J Crohns Colitis. 2017 Jan;11(1):26-34.

• NRAS position paper on biosimilar medicines – revised 2017. National Rheumatoid Arthritis Society. 2017 Jan. Available from: https://www.nras.org.uk/data/files/Publications/2017_NRAS%20Biosmilars%20Position%20Paper.pdf.

References

References• Lakhanpal S. American College of Rheumatology responds to FDA Draft Guidance on Biosimilar

Interchangeability [Press release]. Atlanta (GA): American College of Rheumatology. 2017 May 19 [cited 2020 Jan 21]. Available from: https://www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/810/American-College-of-Rheumatology-Responds-to-FDA-Draft-Guidance-on-Biosimilar-Interchangeability.

• Committee on Rheumatologic Care. American College of Rheumatology position statement: biosimilars [Internet]. Atlanta (GA): American College of Rheumatology. 2018 May 21 [cited 2020 Jan 21]. Available from: https://www.rheumatology.org/Portals/0/Files/Biosimilars-Position-Statement.pdf.

• Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017 Jun;76(6):960-977.

• de Ridder L, Waterman M, Turner D, et al. Use of biosimilars in paediatric inflammatory bowel disease: a position statement of the ESPGHAN Paediatric IBD Porto Group. J Pediatr Gastroenterol Nutr. 2015 Oct;61(4):503-8.

• Hematopoietic Growth Factors, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. 2020 Jan 27. Available from: https://www.nccn.org/.

References• Pahnke S, Egeland T, Halter J, et al; Working Group Medical of the World Marrow Donor Association.

Current use of biosimilar G-CSF for haematopoietic stem cell mobilisation. Bone Marrow Transplant. 2019 Jun;54(6):858-66. Epub 2018 Oct 3.

• Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33:3199-212.

• Duong HK, Savani BN, Copelan E, et al. Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2014;20:1262-73.

• Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. European J Cancer. 2011;47:8-32.

• Choe JY, Prodanovic N, Niebrzydowski J, et al. A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017 Jan;76(1):58-64.

• Smolen JS, Choe JY, Prodanovic N, et al. Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results. Rheumatology (Oxford). 2017 Oct 1;56(10):1771-1779.

References• Smolen JS, Choe JY, Prodanovic N, et al. Safety, immunogenicity and efficacy after switching from

reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study. Ann Rheum Dis. 2018 Feb;77(2):234-240.

• Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministeredwith methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613-20.

• Yoo DH, Racewicz A, Brzezicki J, et al. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Research & Therapy. 2016;18:82.

• Yoo DH, Prodanovic N, Jaworski J, et al. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis. 2017 Feb;76(2):355-63. Epub 2016 Apr 29.

• Waller CF, Tiessen RG, Lawrence TE, et al. A pharmacokinetics and pharmacodynamics equivalence trial of the proposed pegfilgrastim biosimilar, MYL-1401H, versus reference pegfilgrastim. J Cancer Res Clin Oncol. 2018 Jun;144(6):1087-1095.

References• Sorgel F, Schwebig A, Holzmann J, Prasch S, Singh P, Kinzig M. Comparability of biosimilar filgrastim with

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