BIOSIMILARS: How Do They Affect Patient Care and Safety?

Transcription

1 BIOSIMILARS: How Do They Affect Patient Care and Safety? Josie Garnoc, MSN, RN, CRNI, OCN Director of Nursing, Beaumont Hospital-Grosse Pointe Grosse Pointe, Michigan

2 Disclosure Statement Nothing to Disclose

3 Disclosure Statement Nothing to Disclose

4 Objectives What is the definition of a reference product? What is the difference between biosimilar and generic product? What is an interchangeable product? Discuss the FDA evaluation of Biosimilar product and how they might affect patient safety. Discuss the consensus based recommendations related to biosimilars to treat rheumatic diseases.

5 BIOSIMILAR IS NOT A GENERIC

6 FDA Definition -A generic drug is the same as a brand name drug in dosage, safety, strength, how it is taken, quality, performance and intended use.

7 Generic Chemical Structure

8 Biologics Price Competition and Innovation Act of 2009 A biosimilar is a biological product that is highly similar to the reference product notwithstanding minor differences in clinically inactive components and that there are no clinically meaningful difference between the reference product and the biological product in terms of safety, purity, and potency of the product. Volume29 Number3 May 2017

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10 Biological Structure

11 GENERIC small molecule simple, well defined chemical structure, exact replication various route of administration most nonimmunogenic BIOSIMILAR large, complex molecule primary amino acid sequence, similar to originator complex; cultured from living systems IV, IM, SC potentially immunogenic Feldman, Seminars in Arthritis and Rheumatism

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13 Large Molecules bdmards: biological bodmards: bio-originator (reference product: existing, branded biological product) bsdmards: biosimilar

14 FDA Biosimilar Approval Process Stepwise process Totality of evidence; biological structure, amino acid sequence, modifications, product stability/quality, binding affinities, MOA Emphasis comparable PK/PD with the reference product Relevant population with focus on safety/immunogenicity

15 FDA Biosimilar Approval Process At least one phase III clinical comparability trial to confirm similar efficacy/safety in a sensitive population. Null hypothesis: biosimilar is either inferior or superior to reference product based on predetermined equivalence parameters Detection of clinically meaning difference Goal: reject null hypothesis of nonequivalence; accept alternative hypothesis biosimilar/reference product are equivalent

16 FDA Biosimilar Approval Process Differences between the 2 are not clinically and statistically meaningful of primary end point Reference drug and biosimilar within equivalence margin at 90 or 95% CI Phase III long enough duration to reflect disease state and detect any clinically important AE s Results of biosimilar/reference product mirror established endpoints

17 FDA Biosimilar Approval Process Extrapolation: clinical data across indications of reference drug; biosimilar meets requirements for licensure. Extrapolate clinical data for each condition of the sensitive population.

18 Interchangeability FDA would require at least one study with 3 or more switches between reference drug and biosimilar Demonstrate biosimilar has same clinical result for all reference product indications Sponsor provide scientific rationale to extrapolate data support interchangeability PK/PD same, any potential difference, immunogenicity

19 Naming Biosimilars Shared core name with reference product (biooriginator) hyphenated ending to core name ending consists of 4 letter devoid of meaning

20 Approved Biosimilars in US Filgrastim-sndz (Zarixo) Infliximab-dyyb (Inflectra), Infliximab-abda (Renflexis) Etanercept-szzs (Erezi) Adalimumab-atto (Amjevita)

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23 Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases Kay J., et,al, Ann Rheum Dis 2018; 77:

24 OverarchingPrinciples: Treatment choice is a shared decision-making process between patient and rheumatologist Contextual aspects of the healthcare system taken into account Biosimilar is neither more or less effective, nor inferior in safety, to its biooriginator Kay J., et,al, Ann Rheum Dis 2018; 77:

25 Biosimilar Interchangeability (BPCI Act): may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product Interchange might take place more than once No biosimilar yet has sought or received the interchangeable designation non-medical switching encouraged by payers if acquisition cost biosimilar is lower Cohen and Kay, Biosimilars for rheumatoid arthritis, 2017

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29 OverarchingPrinciples Patients & HCP should be informed R/T nature of biosimilars: approval process, safety & efficacy Establish methods to gain reliable pharmacovigilance data to include traceability about biosimilars and bio-originators Kay J., et,al, Ann Rheum Dis 2018; 77:

30 Consensus Recommendations: Biosimilar availability must significantly decrease treatment cost/increase access to optimal therapy. Approved biosimilars can be used to treat appropriate patients in same way as their biooriginators. Antidrug antibodies to biosimilars need not be measured in clinical practice, no clinically significant differences in immunogenicity biosimilars/bio-originators. Biosimilar relevant preclinical and phase I data should be available when phase III data published. Kay J., et,al, Ann Rheum Dis 2018; 77:

31 Consensus Recommendations: Registry assessment of biosimilar should occur when multiple switches are made biosimilar/bio-originator; biosimilar/biosimilar. Switching to or among biosimilars should not be done without informing the patient and their healthcare provider. Kay J., et,al, Ann Rheum Dis 2018; 77:

32 Topics for further discussion: Clinical trials of biosimilars Extrapolation of indications Immunogenicity of biosimilars compared with biooriginators Switching between: biosimilar/bio-originator, biosimilar/biosimilar Kay J., et,al, Ann Rheum Dis 2018; 77:

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39 Realities R/T Biosimilars: -Payers/formulary dictate biosimilar -Payers not approving biosimilar (Aetna) -New start patients -Attribute SX R/T biosimilar -Evidence to support outcomes -Concern R/T copay assistance

40 Integration into Practice: -Nocebo effect: negative equivalence to a placebo effect -Impacts adherence -Perception of biosimilars; low awareness, lack of communication -Attribute SX or physiological changes R/T biosimilar: general, drowsiness, nausea, fatigue, insomnia -Verbal, nonverbal cues from HCP: negative connotations -Patient/physician discussions Rezk, M.F., Treatment outcomes with biosimilars: be aware of the nocebo effect, Rheumatol Ther (2017) 4:

41 Integration into Practice: -Patient/physician discussion; shared decision making; benefits/advantages -Patient expectation of AE s: info R/T clinical trials/case studies -Switching: notify patient at time of switch, reasons for switch -Patient/physician discussions outcomes Rezk, M.F., Treatment outcomes with biosimilars: be aware of the nocebo effect, Rheumatol Ther (2017) 4:

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43 Summary: -Continued development of Biosimilars for increased access for more patients for biologicals (40% US population on a biological) -FDA stepwise approval process related to efficacy/safety -Post-marketing surveillance for AE s -HCP influence patient acceptance; nocebo effect

44 References: Alten, R. & Cronstein, B.N., Clinical trial development for biosimilars, Seminars in Arthritis and Rheumatism,(2015)S2-S8 Cohen, S. & Kay. J., Biosimilars: implications for rheumatoid arthritis, Co-Rheumatology, (2017), 29(3) Feldman, S.R., Inflammatory diseases: integrating biosimilars into clinical practice, Seminars in Arthritis and Rheumatism, ( 2015), Frank, R.G., Friction in the path to use of biosimilar drugs, The New England Journal of Medicine, (2018), Kay, J., et. al., Consensus-based recommendations for the use of biosimilars to treat rheumatologic diseases, Ann Rheum Dis, (2018),77: Khraishi, M., et.al., Biosimilars: a multidisciplinary perspective, Clinical Therapeutics, (2016), 38(5) Markus, R., et.al., Developing the totality of evidence for biosimilars: regulatory considerations and building confidence for the healthcare community, BioDrug, (2017) 31: Rezk, M.F., Treatment outcomes with biosimilars: be aware of the nocebo effect, RheumatolTher (2017) 4: Wright, E. et.al., Demystifying the differences: follow-on biologics, biosimilars, and generics, Supplement to The Journal of Family Medicine, (2017) 66(4)S22-S27 Stevenson, J.G. et. al., Biosimilars: practical considerations for pharmacists, Journal of Pharmacology, (2017), 3(7)