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ABP 501 [United States: AMJEVITA™ (adalimumab-atto); European Union: AMGEVITA® (adalimumab)] is the first approved biosimilar to adalimumab [reference product (RP)], a monoclonal antibody (mAb) targeting tumor necrosis factor-alfa (TNF-α). ABP 501 has received approval for use in indications that adalimumab RP is approved for, except those protected by regulatory exclusivity. A systematic step-wise totality of evidence (TOE) approach formed the basis of approval of ABP 501; this involved methodical accumulation of scientifically robust comparative data supporting similarity in analytical, preclinical, and clinical [pharmacokinetics (PK)], efficacy, safety and immunogenicity) evaluations. As a foundational first step, comprehensive analytical assessments demonstrated that ABP 501 is structurally and functionally similar to adalimumab RP in critical quality attributes. Preclinical assessments confirmed similar activity in assessing mechanisms of action and toxicology. Clinical evaluation included a phase 1 PK equivalence study in healthy subjects and two comparative phase 3 studies that evaluated ABP 501 and adalimumab RP in two sensitive patient populations, plaque psoriasis (PsO) and rheumatoid arthritis (RA). The PK profiles of ABP 501 and adalimumab RP were similar in healthy subjects as well as patients with PsO and RA. The pivotal phase 3 study in patients with PsO demonstrated that ABP 501 was clinically similar to adalimumab RP in terms of efficacy, safety and immunogenicity in both the primary and transition phases. The pivotal phase 3 study in patients with RA also established clinical similarity between ABP 501 and adalimumab RP; an open-label extension of this study demonstrated sustained efficacy over an additional 72 weeks, with no new safety or immunogenicity concerns with ABP 501 treatment. Overall, the TOE supported the conclusion that ABP 501 is highly similar to adalimumab RP and provided scientific justification for extrapolation to all the approved indications of adalimumab RP not protected by exclusivities.Funding: Amgen Inc.

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BackgroundIn clinical practice, patients treated with an originator product may be transitioned to a biosimilar. Therefore, it is important to ensure that such transition is safe and is not associated with increased immunogenicity.ObjectivesTo study the incidence of binding anti-drug antibodies (bADAs) and neutralising anti-drug antibodies (nADAs) after patients with rheumatoid arthritis (RA) are transitioned from adalimumab reference product (RP) to ABP 501, an approved biosimilar for adalimumab.MethodsWe analysed data from the open-label extension (OLE) of a randomised 26 week phase 3 study (NCT 01970475) comparing ABP 501 and adalimumab. In this OLE study (NCT02114931), patients originally randomised to ABP 501 in the parent study continued on ABP 501 while patients originally randomised to adalimumab (RP) were switched to ABP 501 so that all patients received ABP 501. Specifically, we studied the incidence of new ADAs in patients who were ADA negative at the time of entry into the OLE study. The incidence after excluding transiently elevated ADAs was also examined.ResultsThe Table summarises the incidence of ADAs.Abstract THU0198 – Table 1ConclusionsTransitioning from adalimumab reference product to ABP 501 was not associated with increased immunogenicity over the observational period of 72 weeks.Disclosure of InterestE. Krishnan Shareholder of: Amgen Inc., Employee of: Amgen Inc., D. Mytych Shareholder of: Amgen Inc., Employee of: Amgen Inc., N. Zhang Shareholder of: Amgen Inc., Employee of: Amgen Inc., H. Wang Shareholder of: Amgen Inc., Employee of: Amgen Inc., A. Kaliyaperumal Shareholder of: Amgen Inc., Employee of: Amgen Inc.

cytometry, RNAseq, histology and in situ hybridization. Using single-cell RNA sequencing we aim to identify early onset markers of dysplasia and unveil the mechanism of malignant transformation. Results: Gata2 heterozygous mutant mice survive into adulthood without developing signs of alterations in the myeloid lineage. Phenotypic HSCs of these mutant adult mice have unchanged Gata2 expression but are lower in frequency, more proliferative and transcriptionally more committed to differentiation compared to WT. Additionally, they display increased DNA damage indicating these HSCs experience proliferative stress. gata2b+/ − zebrafish show reduced myeloid differentiation and the kidney marrow smears of this aged fish show dysplastic myeloid cells. Summary/Conclusion: Our mouse model doesn't incur a malignancy even though it acquires an HSCs phenotype. Our zebrafish model develops a dysplastic kidney marrow and recapitulates characteristics of the GATA2 deficiency syndromes. Both models can give new insights into the physiopathology of these diseases.