Module 9 2024

05/09/2024

Acceptability of Differences – US Examples (1)

• Differences in formulation which had minor impact on PK accepted 1 • 1 new peak for ABP215 only = sequence variant due to a point mutation Ser121 to Ala stable and <1% not part of the complementarity determining region - ala will not perturb structure because switch from 1 small amino acid to another 2 • Lower level of misformed S-S bonds increased in vitro potency but justified based on S-S reform correctly in vivo 3 • Lower aggregate levels for ABP215 Amgen’s Mvasi (bevacizumab) HMWS 0.3% vs 0.46/7% 4 • Charge variants : ASN30>in US RMP; 2 additional peaks in MYL-1401O related to oxidation at Met 255 and Asn30 deamidation 4

1 Sandoz Zarxio ODAC 2 BLA 761028: ABP215, biosimilar to US-Avastin, ODAC Briefing Document 13 July 2017 3 Sandoz etanercept (Arthritis Adcom Transcript 15/7/16) 4 BLA 761074 ODAC Briefing Document MYL-1401O, biosimilar to US-Herceptin 13 July 2017

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Acceptability of Differences – US Examples (2)

– Slight change in levels of glycans – do not preclude a determination of high similarity ( Amgen’s adalimumab 1 – bevacizumab diff Mann5/6 and sialic acid unlikely to have a clinical impact as bevacizumab has predominantly soluble target 2 – Differences in ADCC accepted – not considered a relevant MoA 3 – greater than 90 percent of lots of the proposed biosimilar are still within the quality range of the reference product 4

1 FDA Arthritis Adcom Slides 14July16 2 4 BLA 761074 ODAC BD MYL-1401O, biosimilar to US-Herceptin 13 Jul 2017

3 Sandoz etanercept: Arthritis Adcom transcript 15July16 4 Celltrion infliximab: Arthritis Adcom transcript 9Feb16.

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