ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2372

Comparison Of Proposed Biosimilar PF-05280586 With Rituximab: Nonclinical and Phase I Clinical Assessments

Dolca Thomas1, Jean-Claude P. Becker2 and Chee-Keng Ng3, 1Biosimilars Research and Development Unit, Pfizer Inc., New York, NY, 2Pfizer Biosimilars Research and Development/Medical Affairs., Pfizer Inc., New York, NY, 3Biotherapeutic Pharmaceutical Sciences, Pfizer Inc., Andover, MA

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy III

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.

Disclosure:

D. Thomas,

Pfizer Inc,

1,

Pfizer Inc,

3;

J. C. P. Becker,

Pfizer Inc,

1,

Pfizer Inc.,

3;

C. K. Ng,

Pfizer Inc,

1,

Pfizer Inc,

3.

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