THE ADVENT OF RITUXIMAB BIOSIMILARS: WHERE ARE WE NOW?

A biosimilar version of rituximab (TruximaTM) has recently been granted approval for the treatment of NHL, CLL, and rheumatoid arthritis (RA) in South Korea.44 Several potential rituximab biosimilars are currently in development, each in comparison with the originator (reference) rituximab (Table 3). A study in patients with newly diagnosed advanced FL showed pharmacokinetic similarity between a potential biosimilar to rituximab, CT-P10, and rituximab (each administered with CVP), with similar B-cell kinetics and immunogenicity.45 In another study, CT-P10 and rituximab showed equivalent pharmacokinetics, and comparable efficacy, pharmacodynamics, immunogenicity, and safety in patients with RA.46 A clinical study in patients with previously untreated FL showed therapeutic equivalence in overall response rate between another proposed biosimilar to rituximab, GP-2013, and rituximab sourced from the EU. In this trial, similarity was demonstrated for efficacy, pharmacokinetic, and pharmacodynamic parameters, with similar safety findings.47 In addition, the efficacy and safety of another potential biosimilar, BI-695500, in patients with low-tumor-burden lymphoma is under clinical investigation (ClinicalTrials.gov, NCT01950273). ABP 798, a potential biosimilar to rituximab, is in clinical development in patients with CD20-positive B-cell NHL (ClinicalTrials.gov, NCT02747043). Another potential biosimilar to rituximab, MabionCD20, is in development in patients with CD20-positive DLBCL (ClinicalTrials.gov, NCT02617485).


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(To view a larger version of Table 3, click here.)

In nonclinical studies, PF-05280586, a proposed biosimilar to rituximab, showed the same primary amino acid sequence and similar physicochemical and in vitro functional properties as the licensed originator biologic.48 A study in patients with active RA demonstrated pharmacokinetic similarity of PF-05280586 to rituximab sourced from the EU (rituximab-EU) and the US (rituximab-US) and that of rituximab-EU to rituximab-US.49 In this trial, all 3 treatments were generally well tolerated, and the incidence of treatment-related adverse events was low. These encouraging findings support the ongoing development of PF-05280586 as a potential biosimilar to rituximab. A trial is ongoing to compare the efficacy, safety, pharmacokinetics, and immunogenicity of PF-05280586 to rituximab in patients with low-tumor-burden FL (ClinicalTrials.gov, NCT02213263).

CONCLUSION

FL accounts for up to 20% of all lymphomas. Debate continues over the optimal treatment strategy for untreated FL: the watch-and-wait approach vs therapeutic intervention. However, for patients who are candidates for systemic therapy, an anti-CD20 monoclonal antibody alone or in combination with chemotherapy remains at the forefront of the therapeutic landscape.

It is well recognized that rituximab will remain as the cornerstone of therapy in the treatment of patients with FL. The loss of exclusivity of composition-of-matter patents of biologics in recent and coming years, and the lack of access to rituximab in some countries are of particular concern for patients and physicians. Thus, it is relevant, appropriate, and necessary to develop a biosimilar to rituximab with the potential to generate cost savings and efficiencies for health care systems and to increase access to patients worldwide, which can help augment resources for other important aspects of health care.

It will be crucial to engage clinicians on the importance of biosimilars, and moreover, to increase understanding of data that underpin the development of biosimilars and how these data may translate into clinical practice. At present, several potential rituximab biosimilars are in development. As a result of extensive studies, the availability of safe and effective rituximab biosimilars is eagerly anticipated, potentially offering a greater range of therapeutic options and improved clinical benefits to patients with FL.

Acknowledgments

Medical writing support was provided by Neel Misra, MSc, of Engage Scientific Solutions, and funded by Pfizer Inc.

Author contributions

All the authors made substantial contributions to conception and design, execution, or analysis and interpretation of data; drafted the article or revised it critically; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

This review was supported by Pfizer Inc. JS has served on advisory boards for Pfizer, Boehringer Ingelheim, and Bristol-Myers Squibb, and on speakers bureaus for Celgene, Boehringer Ingelheim, and Eli Lilly. BD was a full-time employee of Pfizer at the time this manuscript was initiated. IJ is a full-time employee of Pfizer. JC has no conflicts of interests to declare in this work.

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Source: Cancer Management and Research.
Originally published april 24, 2017.