Biosimilar and interchangeable: Inseparable scientific concepts?

Mora, Fernando; Balsa, A.; Cornide-Santos, María; Carrascosa, José Manuel; Marsal, Sara; Gisbert, Javier P.; Abad, M. Martín; Duarte, Rafael F.; Wiechmann, Michael; Martínez, Rafael

doi:10.1111/bcp.14089

Cited by 14 publications

(8 citation statements)

References 20 publications

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“…The interchangeability of a biosimilar (Table 1) for its innovator (or vice versa) is a complex topic that has generated much discussion [1][2][3][4][5][6][7]. Interchangeability is closely linked to nonmedical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons, such as cost (Table 1) [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

et al. 2021

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In the USA, an interchangeability designation provides biosimilar sponsors with a pathway for achieving what is standard for small-molecule generics: pharmacy-level auto-substitution for an innovator. No other major health authority links interchangeability to automatic substitution, as all require the involvement of the prescriber or patient in a medication change. This editorial considers the clinical impact and practicality of auto-substitution. First, interchangeability is linked to non-medical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons. NMS may generate negative sentiment in those unwilling or reluctant to switch, which can adversely impact treatment outcomes (i.e., nocebo effect). Indeed, in real-world studies of tumor necrosis factor inhibitors, discontinuation rates have been shown to be higher in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators. Second, interchangeability may impede pharmacovigilance and traceability, as not all jurisdictions require innovators and biosimilars to have distinct biologic names. Third, an interchangeability designation from the US Food and Drug Administration only permits a biosimilar to be automatically substituted for its innovator, not other biosimilars (if available). Pharmacist education would be needed to avoid off-label, automatic substitution among biosimilars of a single innovator. Last, once granted, an interchangeability designation exists in perpetuity under current US federal law. However, the supply chains of innovators and biosimilars are maintained independently, with no requirement for reconfirmation of biosimilarity or interchangeability. We feel that additional guidance is needed for the auto-substitution of biosimilars and innovators to become a reality.

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Section: Introductionmentioning

confidence: 99%

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

et al. 2021

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“…Finally, the results from this systematic literature search are generally in line with the RWE with CT-P13 in large switching studies, such as the NORSWITCH and DANBIO registries, and systematic literature searches of biosimilar switching studies, including infliximab biosimilars and post-marketing surveillance of infliximab biosimilars [36,37]. There is currently no data suggesting that the risk of switching to a biosimilar in terms of increased immunogenicity is higher than switching between two batches of any biologic [38,40].…”

Section: Discussionmentioning

confidence: 62%

A Systematic Review on Infliximab Biosimilar SB2: From Pre-Clinical Data to Real-World Evidence

Macaluso

Cummings

Atreya

et al. 2022

Expert Opinion on Biological Therapy

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Introduction:The infliximab biosimilar SB2 was approved in the EU (2016, Flixabi ® ) and the US (2017, Renflexis ® ) for the same indications as the reference product (Remicade ® ) based on a robust analytical and clinical data package.Areas covered: This systematic literature review summarizes available analytical and clinical data on SB2, including randomized controlled clinical trials and real-world evidence studies. Overall, 184 articles and congress abstracts were identified (excluding duplicates), whereof 5 reports on analytical data, four reports on two randomized controlled trials and 13 reports of real-world evidence studies were included. Expert opinion:The available analytical and clinical data support the equivalence of SB2 to the reference product across approved indications. This is further supported by emerging real-world evidence, particularly in extrapolated indications such as inflammatory bowel disease for both infliximab-naïve patients and patients already established on infliximab switching to SB2. Switching from originator or biosimilar infliximab to SB2 including both single and multiple switches was not associated with an increased risk of loss of treatment response or any safety or immunogenicity concerns. Overall, the approved infliximab biosimilar SB2 is safe and effective in clinical practice across licensed indications.

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“…An originator biologic is a complex molecule with many post-translational modifications, resulting in multiple different forms and batch-to-batch variability [ 19 ]. Unlike traditional generic non-biologics, such originator products are too complicated to duplicate faithfully.…”

Section: Discussionmentioning

confidence: 99%

Efficacy, Safety and Immunogenicity of AVT02 Versus Originator Adalimumab in Subjects with Moderate to Severe Chronic Plaque Psoriasis: A Multicentre, Double-Blind, Randomised, Parallel Group, Active Control, Phase III Study

Feldman

Reznichenko²,

Pulka

et al. 2021

BioDrugs

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Background AVT02 (adalimumab) is a proposed biosimilar to Humira ® . AVT02 is produced at a 100 mg/mL concentration with a citrate-free formulation. Objectives The aim of this study was to compare the efficacy, safety and immunogenicity of AVT02 versus Humira ® in subjects with moderate to severe chronic plaque psoriasis. Methods This double-blind, randomised, parallel group, active control study of adult subjects compared (at a 1:1 ratio) AVT02 with originator adalimumab 80 mg subcutaneously in Week 1, then 40 mg every other week. At Week 16, subjects who had received originator adalimumab were re-randomised at a 1:1 ratio to continue receiving originator adalimumab, or to switch to AVT02, every other week until Week 48, with final efficacy endpoint at Week 50. Subjects who initially received AVT02 continued to receive AVT02 from Week 16 to Week 48. The primary endpoint was percentage improvement in Psoriasis Area and Severity Index (PASI) score at Week 16. Secondary efficacy endpoints included percentage improvement in PASI score at additional timepoints, change from baseline in Dermatology Life Quality Index (DLQI) score and number and percentage of subjects achieving static Physician’s Global Assessment (sPGA) responses of ‘clear’ or ‘almost clear’. Additional secondary endpoints included comparison of adverse event profiles, anti-drug antibodies and neutralising antibodies, and serum trough levels of adalimumab at steady state. Results A total of 413 subjects were randomised (205 to AVT02 and 208 to originator). The percentage improvement in PASI score at Week 16 was 91.6% for AVT02-treated subjects and 89.6% for originator adalimumab. The 90% confidence intervals for the primary endpoint were within the pre-defined equivalence margin of ±10% (90% CI − 0.76 to 5.29; 95% CI − 1.34 to 5.88), and a comparable pattern for DLQI score (11.4-point and 10.6-point improvement in AVT02-treated and originator adalimumab-treated groups, respectively) and sPGA (90.5% in both groups achieving ‘clear’ or ‘almost clear’) at Week 16 supported the assessment. Efficacy persisted through Week 50 of the study in all treatment groups, including those who switched from originator adalimumab to AVT02, for percent improvement in PASI score, quality-of-life assessment and sPGA. The safety, tolerability and immunogenicity profiles between AVT02 and originator adalimumab were similar at Week 16, and this persisted in the switched and continued groups through Week 50. Conclusion Objective and subjective measures of efficacy supported the evaluation of biosimilarity between AVT02 and originator adalimumab at Week 16 and until Week 50, in switched and continued treatment groups. AVT02 was safe and well tolerated, with a safety and immunogenicity profile similar to that observed in originator adalimumab with no clinically meaningful difference between the ...

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Biosimilar and interchangeable: Inseparable scientific concepts?

Cited by 14 publications

References 20 publications

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

A Systematic Review on Infliximab Biosimilar SB2: From Pre-Clinical Data to Real-World Evidence

Efficacy, Safety and Immunogenicity of AVT02 Versus Originator Adalimumab in Subjects with Moderate to Severe Chronic Plaque Psoriasis: A Multicentre, Double-Blind, Randomised, Parallel Group, Active Control, Phase III Study

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