935P - Development of PF-05280586, a potential biosimilar to rituximab

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Haematologic Malignancies
Presenter Ira Jacobs
Citation Annals of Oncology (2016) 27 (6): 313-327. 10.1093/annonc/mdw375
Authors I. Jacobs1, L.A. Melia2, C. Kirchhoff3, C. Kobryn4, P. Nava-Parada1, J. Rosenberg5, A.M. Ryan6, D. Yin7
  • 1Global Medical Affairs, Pfizer Inc., 10017-5755 - New York/US
  • 2Biotechnology Clinical Development, Pfizer Inc, San Diego/US
  • 3Global Technology Services Biotechnology And Aseptic Sciences, Pfizer Inc, 63017 - Chesterfield/US
  • 4Biosimilars Regulatory Strategy, Pfizer Inc, 06430 - Groton/US
  • 5Pfizer Global Research And Development, Pfizer Inc, 06430 - Groton/US
  • 6Drug Safety Research And Development, Pfizer Inc, 06430 - Groton/US
  • 7Clinical Pharmacology, Pfizer Inc., San Diego/US

Abstract

Background

PF-05280586 is being developed as a potential biosimilar to rituximab. Similarity of PF-05280586 to rituximab sourced from the EU and US (rituximab-EU and -US) was assessed using structural, functional, nonclinical pharmacokinetic (PK), tolerability, and toxicity studies, and clinical studies.

Methods

Structural similarity was determined by peptide mapping and other analytical methods. Functional similarity was measured using complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis. Pharmacodynamic (PD) effects of PF-05280586 and rituximab-EU on B-cell repletion were compared in sexually mature cynomolgus monkeys in single-dose PK and repeat-dose toxicity studies. In a clinical study, 220 patients with active rheumatoid arthritis on a background of methotrexate and inadequate response to one or more tumour necrosis factor–antagonist therapies were randomized to intravenous PF-05280586, rituximab-EU or rituximab-US 1000 mg on study days 1 and 15 to assess PK similarity; PD, safety, tolerability, and immunogenicity were also evaluated.

Results

State-of-the-art characterization methods show PF-05280586 has similar structure and function to rituximab-EU and rituximab-US. Nonclinical results indicated PK, PD, and in vivo findings of PF-05280586 are similar to rituximab-EU. In patients, PF-05280586, rituximab-EU, and rituximab-US exhibited similar clinical PK profiles; the 90% confidence intervals of test-to-reference ratios were within the bioequivalence margin of 80.00–125.00%. All treatments resulted in rapid and profound reduction of CD19+ B-cells and sustained profound B-cell suppression through week 25. No clinically meaningful differences in adverse events or immunogenicity were identified.

Conclusions

Evaluation of PF-05280586 thus far supports its development as a potential biosimilar to rituximab. A randomized clinical trial comparing efficacy, safety, PK, and immunogenicity of PF-05280586 monotherapy to rituximab-EU monotherapy in treatment-naïve patients with CD20 + , low tumour burden follicular lymphoma is ongoing.

Clinical trial identification

NCT01526057 and NCT02213263.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

I. Jacobs, L.A. Melia, C. Kirchhoff, C. Kobryn, P. Nava-Parada, J. Rosenberg, A.M. Ryan, D. Yin: Full time employee of Pfizer Inc and stock ownership and/or options from Pfizer Inc.