A phase I/II study of Pfizer’s rituximab biosimilar candidate PF-05280586 has shown similar pharmacokinetic (PK) properties, according to Jacobs and co-authors [1].
The originator product, Roche’s blockbuster drug MabThera/Rituxan (rituximab), was approved by the US Food and Drug Administration (FDA) in November 1997 and by the European Medicines Agency (EMA) in June 1998 [1]. MabThera is indicated for the treatment of rheumatoid arthritis, non-Hodgkin lymphoma and lymphocytic, chronic, B-cell leukaemia.
The randomized, double-blind study compared the PK, pharmacodynamics (PD) and safety of PF-05280586 and rituximab sourced from the European Union (rituximab-EU) and the US (rituximab-US) in subjects with active rheumatoid arthritis with an inadequate response to TNF inhibitors (REFLECTIONS B328-01). Subjects were randomized 1:1:1 to one course of intravenous PF-05280586, rituximab-US, or rituximab-EU 1,000 mg on Day 1 and Day 15.
The study, which was carried out in Australia, Canada, Colombia, Germany, Israel, Mexico, Russia, South Africa, the UK and the US, enrolled 220 patients. The primary endpoints were the PK parameters maximum concentration (Cmax) and area under the time-concentration curve (AUC0-∞) at week 25. Secondary endpoints included AUC0-T, CD19+ B-cell count and circulating IgM, change from baseline in Disease Activity Score 28 - C-reactive protein (DAS28-CRP), change from baseline in American College of Rheumatology 20% response criteria (ACR20), ACR50, and ACR70 response, Health Assessment Questionnaire and detection of anti-drug antibodies (ADA).
The authors claimed that ‘the primary objective of demonstrating PK similarity among the PF-05280586, rituximab-US, and rituximab-EU was achieved based on the 80-125% bioequivalence criteria’. The authors also reported that ‘although not designed to demonstrate similarity for efficacy, mean DAS28-CRP, 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’. All treatments resulted in rapid CD-19+ B-cell depletion by Week 2, which was sustained for the study duration. Safety and ADAs were also similar among treatment arms.
The authors concluded that ‘improvement in clinical response occurred with PF-05280586, rituximab-US, and rituximab-EU’, that ‘all three treatments had similar PD effect on CD19+ B-cell’, and that ‘all treatments were generally well-tolerated with similar AE profiles’.
According to ClinicalTrials.gov Pfizer is currently recruiting participants for a phase III trial in patients with CD20-positive, low tumour burden, follicular lymphoma (REFLECTIONS B328-06).
The patents on MabThera/Rituxan already expired in Europe in February 2013 and expire in the US in September 2016 [1]. Although many companies are still working on biosimilars of rituximab [2], in recent years several companies have halted their rituximab programmes [3].
Conflict of interest
The authors of the abstract [1] are all employees of Pfizer and some are also shareholders of Pfizer. For full details of the authors conflicts of interest see the abstract [1].
Editor’s comment
It should be noted that data of the study presented in this article were published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
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References
1. GaBI Online - Generics and Biosimilars Initiative. Biological patent expiries [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Oct 30].
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of rituximab [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Oct 30]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-of-rituximab
3. GaBI Online - Generics and Biosimilars Initiative. Boehringer Ingelheim stops biosimilar rituximab development [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Oct 30]. Available from: www.gabionline.net/Biosimilars/News/Boehringer-Ingelheim-stops-biosimilar-rituximab-development
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