Session Type: Abstract Submissions (ACR)
Background/Purpose: PF-05280586 is being developed as a potential biosimilar to rituximab, a monoclonal antibody (mAb) approved for the treatment of moderate-to-severe rheumatoid arthritis and lymphomas. The purpose is to present data demonstrating the structural and functional similarity of PF-05280586 to rituximab in nonclinical studies and pharmacokinetic (PK) and pharmacodynamic (PD) similarity in the first clinical study that has completed recruitment and dosing.
Methods: Nonclinical Studies: Structural similarity of PF-05280586 and rituximab-EU (MabThera®) was determined by side-by-side comparisons of peptide maps. In vitro functional similarity was determined with complement-dependent cytotoxicity (CDC) and antibody-dependent cell cytotoxicity (ADCC) assays using the Ramos B lymphoblastoid cell line as the target. Similarity of interaction with receptors was determined using SPR system.
Clinical Trial: A phase1/2 clinical trial (NCT 01526057) in patients with active rheumatoid arthritis (RA) is in progress to determine PK and PD similarity between PF-05280586 and the two marketed formulations of rituximab from the US (rituximab-US; Rituxan®) and the EU (rituximab-EU; MabThera®).
Results: Nonclinical Studies: The peptide map of PF-05280586 was similar to that of rituximab-EU indicating amino acid identity between the two mAbs. The dose-response curves of the 2 mAbs in the CDC and ADCC assays were essentially superimposable indicating similar in vitro function. Similarly, the binding to FcγRIIIa (158V) of PF-05280586 coincided with that of rituximab-EU, indicating similar mechanisms of actions of the two mAbs.
Clinical Trial: A total of 220 patients with active RA have been randomized into 3 arms and dosed. Monitoring for safety by an independent committee has shown no safety signals. The anticipated trial completion is Q42013.
Conclusion: PF-05280586 showed in vitro structural and functional similarity to rituximab-EU. PF-05280586 and rituximab appear to be well tolerated in nonclinical and clinical studies. These results support the development of PF-05280586 as a proposed biosimilar to rituximab.
J. C. P. Becker,
C. K. Ng,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-proposed-biosimilar-pf-05280586-with-rituximab-nonclinical-and-phase-i-clinical-assessments/