Background/Purpose: PF-06438179, a proposed biosimilar to infliximab, was evaluated for immunogenicity in a phase 1 pharmacokinetic (PK) similarity study.

Methods: In this double-blind trial (NCT01844804), 151 healthy volunteers aged 18-55 years were randomized 1:1:1 to 1 of 3 treatment groups, of which 146 received a single 10 mg/kg intravenous dose of PF-06438179 (n=49), infliximab sourced from the US (infliximab-US; n=49), or infliximab sourced from the EU (infliximab-EU; n=48). All subjects provided informed consent and were evaluated post dose for safety and immunogenicity over 12 weeks, and for PK over 8 weeks. Serum samples for detecting anti-drug antibodies (ADA) and neutralizing antibodies (NAb) were collected at 0, 336, 672, 1008, 1344, and 2016 hours post dose. ADA samples were analyzed using 2 validated electrochemiluminescent immunoassays, 1 each to detect antibodies against PF-06438179 and reference drugs (infliximab-US or -EU).  A tiered approach of screening, confirmation and titer quantitation was utilized. Samples were first tested for antibodies against the dosed product and confirmed ADA positive samples were then tested for ADA cross-reactivity using the alternate assay. ADA positive samples were also analyzed for NAb using a validated semi-quantitative cell-based assay against the dosed product and for NAb cross-reactivity using the alternative NAb assay. 

Results: Samples for immunogenicity assessment were collected from all 146 subjects. No subjects tested positive for ADA at baseline. Six (16.2%), 14 (32.6%) and 11 (28.2%) subjects in the PF-06438179, infliximab-EU, and infliximab-US groups, respectively, had ≥1 ADA-positive sample through Day 85. Twenty-seven of the 31 subjects (6/6 in PF-06438179, 10/14 in infliximab-EU, and 11/11 in infliximab-US) that tested positive for ADA also tested positive for cross-reactivity by the alternative assay, suggesting that anti-drug antibodies were likely developed against epitopes shared among the study drugs. Of the 31 subjects who tested positive for ADA, 26 tested positive for NAb (5/6 in PF-06438179; 12/14 in infliximab-EU; 9/11 in infliximab-US). Overall safety profiles were similar across the 3 study drugs and no infusion related reactions were reported. The 3 study drugs demonstrated PK similarity, based on the 90% confidence intervals of the test-to-reference ratios for maximum observed serum concentration (C_max), area under the serum concentration-time profile from time 0 to the time of last quantifiable concentration (AUC_t), and area under the serum concentration-time profile from time 0 extrapolated to infinite time (AUC_inf) each falling within the standard bioequivalence region of 80-125%.

Conclusion: The 3 study drugs had comparable immunogenicity profiles with a somewhat lower incidence of ADA response in the PF-06438179 group. The majority of ADA-positive subjects also developed NAb. Overall, PF-06438179 demonstrated PK similarity and comparable safety and immunogenicity profiles to infliximab in healthy subjects. Further comparative assessment of immunogenicity for PF-06438179 will be carried out in a planned phase 3 trial in patients with rheumatoid arthritis.

Study supported by Pfizer Inc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunogenicity-assessment-of-pf-06438179-a-potential-biosimilar-to-infliximab-in-healthy-volunteers/