Japanese regulation of biosimilar products: past experience and current challenges

Arato, Teruyo

doi:10.1111/bcp.12931

Cited by 32 publications

(25 citation statements)

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“…The Japanese regulatory authority [the Pharmaceuticals and Medical Devices Agency (PMDA)] published guidelines on biosimilars, known as “follow-on biological products” (FOBPs) in Japan, in 2009 [ 11 – 13 ]. According to the PDMA, a follow-on biological product is a new biotechnological medicinal product developed to be similar to an already licensed, biotechnology medical product.…”

Section: Discussionmentioning

confidence: 99%

A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

Hanes

Chow

Pan

et al. 2018

Cancer Chemother Pharmacol

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PurposeAnalytic, pharmacokinetic (PK), and clinical similarity between the biosimilar ABP 215 and bevacizumab has previously been demonstrated in global studies. Here we present a phase 1 study in healthy adult Japanese men.MethodsThis study was a randomized, single-blind, single-dose, parallel-group study comparing PK parameters of ABP 215 versus EU-authorized bevacizumab in healthy Japanese men. Primary endpoints were maximum observed serum concentration (Cmax) and area under the serum concentration—time curve from time 0 to infinity (AUCinf). Secondary endpoints included AUC from time 0 to time of last quantifiable concentration (AUClast), safety, tolerability, and immunogenicity.ResultsBaseline characteristics were similar among study subjects (n = 24/group). After a 3-mg/kg intravenous infusion, the geometric means (GMs) of Cmax, AUCinf, and AUClast were 71.2 µg/mL, 25,259 µg h/mL, and 22,499.3 µg h/mL, respectively, for ABP 215 and 70.16 µg/mL, 25,801 µg h/mL, and 22,604.6 µg h/mL, respectively, for bevacizumab. The GM ratios (90% confidence interval; CI) for Cmax, AUCinf, and AUClast were 1.015 (0.946–1.088), 0.979 (0.914–1.049), and 0.995 (0.941–1.053) for ABP 215 versus bevacizumab. All CIs fell within the prespecified bioequivalence margin (0.80–1.25). Adverse events (AEs) occurred in 2/24 subjects receiving ABP 215 and 1/24 receiving bevacizumab. There were no deaths or AEs leading to study discontinuation; no subject was positive for binding anti-drug antibodies (ADAs).ConclusionsABP 215 and bevacizumab showed PK similarity in Japanese men. Safety profiles were comparable between the two groups. The pharmacokinetics in Japanese subjects were consistent with those in a previous global PK equivalence study.

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Section: Discussionmentioning

confidence: 99%

A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

Hanes

Chow

Pan

et al. 2018

Cancer Chemother Pharmacol

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“…Our work is focused on clinical development in Europe. For information on clinical biosimilar development in practice in other highly regulated markets, we refer the reader to, for example, Arato for Japan or Hung et al . for the US.…”

Section: Introductionmentioning

confidence: 99%

An update on the clinical evidence that supports biosimilar approvals in Europe

Mielke

Jilma

Jones

et al. 2018

Brit J Clinical Pharma

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AimSponsors and regulators have more than 10 years of experience with the development of biosimilars in Europe. However, the regulatory pathway is still evolving. The present article provides an update on biosimilar development in practice by reviewing the clinical development programmes of recently approved biosimilars in Europe.MethodsWe used the European public assessment reports (EPARs) which are published by the European Medicines Agency (EMA) for a comparison of the clinical development programmes of the 37 approved biosimilars in Europe. Here, we present novel strategies in the development of biosimilars by focusing specifically on the 17 biosimilars that have gained approval in the last year, but we also compare additional key characteristics for all approved biosimilars.ResultsThe high variability of the clinical development strategies that we found previously was confirmed in the present analysis. Compared with earlier biosimilar applications, more nonstandard development strategies have been used recently. This includes, for example, applications without any studies in patients, and more complex study designs. During this study, we found that the EPARs for biosimilars seem to be improving; however, we identified important details which were still often missing. We provide a proposal for a checklist of the minimum information that should be included in biosimilar EPARs for giving the general public insights into the rationale for the approval of biosimilars.ConclusionsEuropean regulators still seem to be open to consider approaches that differ from the guidelines or previous applications, as long as justification is provided.

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“…However, in acknowledgement of the challenges and costs associated with conducting clinical trials using RP sourced from multiple regions, regulatory agencies in the US and EU have provisions for using foreign-sourced comparators in clinical studies if a scientific rationale or "scientific bridge" is established [4,9]. According to the Japanese regulatory guidelines, the use of foreign-approved RPs is acceptable in clinical evaluations if Japanese patients are included in either a comparative PK or comparative clinical efficacy study [14][15][16].…”

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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Japanese regulation of biosimilar products: past experience and current challenges

Cited by 32 publications

References 5 publications

A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

An update on the clinical evidence that supports biosimilar approvals in Europe

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

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