ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1502

A Phase I Trial Comparing PF-05280586 (A Potential Biosimilar) and Rituximab in Subjects with Active Rheumatoid Arthritis

Jean-Claude P. Becker1, Donghua Yin2, Lisa Ann Melia3, Ruifeng Li4, Barry Gumbiner5, Dolca Thomas6, George Spencer-Green7 and Xu Meng2, 1Pfizer Biosimilars Research and Development/Medical Affairs., Pfizer Inc., New York, NY, 2Clinical Pharmacology/Pharmacometrics, Pfizer Inc., San Diego, CA, 3Biotechnology Clinical Development, Pfizer Inc., San Diego, CA, 4Biostatistics, Pfizer Inc., Cambridge, MA, 5Worldwide Research and Development, Pfizer Inc., San Diego, CA, 6Biosimilars Research and Development Unit, Pfizer Inc., New York, NY, 7Worldwide Research and Development, Pfizer Inc., Cambridge, MA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Novel therapies, Biosimilars, Strategies and Mechanisms in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: PF-05280586, a proposed biosimilar to rituximab, has the same primary amino acid sequence as rituximab with similar physicochemical and in vitro functional properties. This pharmacokinetic (PK) similarity study in subjects with active rheumatoid arthritis on a background of methotrexate who had an inadequate response to one or more TNF antagonist therapies (NCT01526057) also evaluated the clinical response and safety of PF-05280586, and rituximab sourced from the US (rituximab-US) and EU (rituximab-EU). Methods: 220 subjects were randomized 1:1:1 to one course of IV PF-05280586, rituximab-US or rituximab-EU 1000 mg (with stable background regimen of methotrexate) on Days 1 and 15. Clinical response was assessed via Disease Activity Score in 28 joints-C-reactive protein (DAS28-CRP) and American College of Rheumatology (ACR) assessments. After Week 17, subjects could enroll in an extension study and receive additional courses of treatment. Results: Baseline demographics were generally similar among the treatment arms. The primary endpoint of PK similarity among the three treatment arms was achieved. Measures of disease activity were numerically higher at baseline among patients randomized to rituximab-US (Table). Although not designed to demonstrate similarity for efficacy, mean DAS28-CRP (Figure), mean number of tender/painful joint counts, mean number of swollen joint counts, and mean high-sensitivity C reactive protein values decreased over time, and improvement in ACR20, ACR50, and ACR70 scores were seen in all groups. The safety profile was similar among treatment arms. A total of 10 subjects experienced SAEs (rituximab-US: 4; PF-05280586: 5; rituximab-EU: 1). Conclusion: In this PK similarity study, a robust improvement in clinical response occurred with PF-05280586, rituximab-US, and rituximab-EU. All 3 treatments were generally well tolerated with a low incidence of treatment-related AEs. Role of the Study Sponsor: Study supported by Pfizer Inc.

Table. Baseline disease characteristics

Mean (SD)

Rituximab-US

n=73

Rituximab-EU

n=74

PF-05280586

n=73

Swollen joint count (28)

14.1 (5.92)

13.0 (6.53)

11.7 (5.36)

Tender/painful joint count (28)

18.1 (6.45)

14.9 (6.79)

14.6 (6.70)

Swollen joint count (66)

19.3 (8.73)

17.8 (10.56)

15.6 (8.91)

Tender/painful joint count (68)

30.4 (15.33)

23.3 (13.23)

22.9 (12.46)

HAQ-DI score

1.75 (0.62)

1.59 (0.54)

1.65 (0.57)

Serum hsCRP (mg/L)

18.17 (24.80)

14.80 (17.42)

12.70 (15.28)

DAS28-CRP

6.22 (0.89)

5.79 (0.95)

5.68 (0.86)

hsCRP=high-sensitivity C reactive protein; DAS28-CRP=Disease Activity Score in 28 joints – C-reactive protein; HAQ-DI=Health Assessment Questionnaire – Disability Index; SD=standard deviation

  Figure. Mean (±SE) DAS28-CRP score over time  

Disclosure:

J. C. P. Becker,

Pfizer Inc.,

1,

Pfizer Inc.,

9;

D. Yin,

Pfizer Inc.,

1,

Pfizer Inc.,

3;

L. A. Melia,

Pfizer Inc.,

3;

R. Li,

Pfizer Inc.,

1,

Pfizer Inc.,

3;

B. Gumbiner,

Pfizer Inc.,

1,

Pfizer Inc.,

3;

D. Thomas,

Pfizer Inc.,

1,

Pfizer Inc.,

3;

G. Spencer-Green,

Pfizer Inc.,

3;

X. Meng,

Pfizer Inc.,

3.

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