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Biosimilars as Partners in Oncology: Expert Guidance on Understanding and Incorporating Biosimilar Agents in Real-World Care

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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.

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Biosimilars as Partners in Oncology: Expert Guidance on Understanding and Incorporating Biosimilar Agents in Real-World Care

  1. 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. 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. 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. 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. 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

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