Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community

Márkus, Richard; Liu, Jennifer; Ramchandani, Monica; Landa, Diana; Born, Teresa L.; Kaur, Primal

doi:10.1007/s40259-017-0218-5

Cited by 84 publications

(109 citation statements)

References 30 publications

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“…Ist nachgewiesen, dass bei einer weiteren Indikation der Wirkmechanismus des Biosimilars gleich ist wie in der untersuchten Indikation (und liegen oben genannte Daten zu Pharmakokinetik, Immunogenität, Wirksamkeit und Sicherheit vor) kann die Zulassung für diese weitere Indikation erfolgen. Dies wird als Konzept der Extrapolation bezeichnet [3,4,6,7].…”

Section: Introductionunclassified

Trastuzumab Biosimilars in the Therapy of Breast Cancer – “Real World” Experiences from four Bavarian University Breast Centres

Hester

Gaß

Fasching

et al. 2020

Geburtshilfe Frauenheilkd

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Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, biosimilar antibodies for breast cancer have found their way into the area of gynaecological oncology. The switch of anti-human epidermal growth factor receptor 2 (HER2) therapy from the reference drug Herceptin® to a biosimilar has presented challenges to the clinics. In addition to structural and organisational measures, training of employees as well as patient briefing and acceptance were major challenges. The study presented here records – within the context of quality assurance – how the switch to a trastuzumab biosimilar was implemented at four Bavarian university clinics in the Purchasing Association of Bavarian University Pharmacies. Materials/Methods Questionnaires on treatment figures and the switching process were sent to breast centres and pharmacies of four Bavarian university clinics between July and December 2019. The neoadjuvant, adjuvant and metastasised anti-HER2 therapy with trastuzumab with or without pertuzumab was recorded, evaluated and summarised. Results In the anti-HER2-therapy, trastuzumab was used intravenously (i. v.) and subcutaneously. Between July and December 2018, all four clinics in the Purchasing Association switched the i. v. trastuzumab therapy from the reference drug (Herceptin) to a biosimilar (for 2018: Kanjinti®). Over 200 patients were treated with trastuzumab i. v. in each of the two half-years of 2018 (before and after the switch). The spectrum of side effects and pCR rates under therapy with the biosimilar were comparable to the experiences made with the reference drug. Three out of four clinics provided training to employees and informed patients by means of a defined information leaflet. Patient acceptance was high. Summary The anti-HER2 therapy could be switched successfully and safely to trastuzumab biosimilars at the Bavarian university hospitals. This may serve as guideline for the further implementation of biosimilars. The structures necessary for this initial switching process have been prepared with trastuzumab as an example.

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Section: Introductionunclassified

Trastuzumab Biosimilars in the Therapy of Breast Cancer – “Real World” Experiences from four Bavarian University Breast Centres

Hester

Gaß

Fasching

et al. 2020

Geburtshilfe Frauenheilkd

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“…The regulatory pathways for biosimilars that apply in the EU and US rely on a totality of evidence approach, comprising a stepwise pathway that shows structural similarity and functional equivalence between the proposed biosimilar and the innovator biologic, coupled with clinical pharmacokinetic (PK) and pharmacodynamic (PD) equivalence studies to confirm similar efficacy, safety, and immunogenicity. 26 The pathways that apply in the EU and US are aligned with WHO guidance for the evaluation of similar biotherapeutic products, 5 and none of the ICs described here has been subjected to such a stringent regulatory assessment. In countries where they are available, many patients who were previously receiving Enbrel Ò may have been switched to an IC (often for nonclinical reasons), and therefore the potential risk that lack of efficacy, immunogenicity, or allergic manifestations may arise from these differences in characteristics cannot be overlooked.…”

Section: Discussionmentioning

confidence: 99%

Variability of intended copies for etanercept (Enbrel®): Data on multiple batches of seven products

Hassett

Scheinberg

Castañeda‐Hernández

et al. 2017

mAbs

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Fusion protein and monoclonal antibody-based tumor necrosis factor (TNF) inhibitors represent established treatment options for a range of inflammatory diseases. Regulatory authorities have outlined the structural characterization and clinical assessments necessary to establish biosimilarity of a new biotherapeutic product with the innovator biologic drug. Biologic products that would not meet the minimum World Health Organization's standard for evaluation of similar biotherapeutic products are available in some countries; in some cases relevant data to assess biosimilarity and appropriate regulatory approval pathways are lacking. Batches of seven intended copy (IC) products for etanercept (Enbrel®) were subjected to a subset of test methods used in the routine release and heightened characterization of Enbrel®, to determine key attributes of identity, quality, purity, strength, and activity. While a number of quality attributes of the IC lots tested met the release specifications for Enbrel®, none fell within these limits across all methods performed, and there were no IC lots that satisfied the criteria typically applied by the innovator to support comparability with Enbrel®. Although the consequences of these differences are largely unknown, the potential for unanticipated clinical outcomes should not be overlooked.

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“…This is followed by preclinical assessments and clinical pharmacology (pharmacokinetics [PK] and pharmacodynamics [PD]) evaluations and, finally, comparative clinical evaluation of efficacy, safety, and immunogenicity between the proposed biosimilar and the RP ( Fig. 1) [4][5][6][7][8][9][10].…”

Section: Step-wise Development Of Biosimilars and Approval Pathwaymentioning

confidence: 99%

Totality of Scientific Evidence in the Development of ABP 980, a Biosimilar to Trastuzumab

Kolberg

Colleoni

Santi³

et al. 2019

Targ Oncol

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ABP 980 was developed as a biosimilar to trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), that is indicated for the treatment of HER2-positive metastatic breast cancer, early breast cancer (EBC), and metastatic gastric cancer. ABP 980 is approved in the United States, European Union, and Japan for all the indications of trastuzumab, based on the totality of evidence (TOE) gathered by the systematic step-wise accumulation of comparative analytical, preclinical, and clinical (pharmacokinetics [PK], efficacy, safety and immunogenicity) data for ABP 980 and trastuzumab reference product (RP). As a key first step of the ABP 980 biosimilar program, comprehensive analytical characterization of critical quality attributes established that ABP 980 is structurally and functionally similar to trastuzumab RP. Complementing these data, results of non-clinical pharmacology, toxicology, and toxicokinetic studies supported similarity between ABP 980 and trastuzumab RP. A randomized study in healthy subjects demonstrated clinical PK equivalence of ABP 980 relative to trastuzumab RP in these subjects. In the final clinical evaluation step, a randomized comparative study (LILAC) confirmed the lack of clinically meaningful differences between ABP 980 and trastuzumab RP in efficacy, safety, and immunogenicity in women with HER2-positive EBC in the neoadjuvant-adjuvant setting. Neoadjuvant EBC represented a sensitive homogenous population for biosimilar demonstrations, and the primary endpoint of pathologic complete response served as a sensitive surrogate endpoint. An important aspect of the LILAC study design is that it is the only study that evaluated the effect of switching from the trastuzumab RP to a trastuzumab biosimilar during the adjuvant phase. No new or unexpected safety signals emerged in the clinical evaluations, with the safety profile of ABP 980 consistent with that previously described for trastuzumab. Overall, the TOE data generated for ABP 980 support the conclusion that it is highly similar to trastuzumab RP, thus providing the scientific justification for extrapolation to all the approved indications of trastuzumab.

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Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community

Cited by 84 publications

References 30 publications

Trastuzumab Biosimilars in the Therapy of Breast Cancer – “Real World” Experiences from four Bavarian University Breast Centres

Trastuzumab Biosimilars in the Therapy of Breast Cancer – “Real World” Experiences from four Bavarian University Breast Centres

Variability of intended copies for etanercept (Enbrel®): Data on multiple batches of seven products

Totality of Scientific Evidence in the Development of ABP 980, a Biosimilar to Trastuzumab

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