Clinical trials are a final step of biosimilar development. In this international multicentre study, appropriately designed with a sensitive primary endpoint and conducted in a sensitive population, rituximab biosimilar BCD-020 goes head-to-head with its reference product.
Rituximab induces lysis of B cells expressing this surface antigen and has revolutionized treatment against B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia. However, because the high cost has limited patient access to this highly demanded treatment in many parts of the world, rituximab biosimilar development is warranted. BCD-020 is a proposed biosimilar with analogous molecular structure and quality characteristics to reference rituximab, as shown preclinically in vitro and in vivo. To compare clinical safety and efficacy of BCD-020 versus reference rituximab given as monotherapy, an international, multicentre, randomised phase III study was performed in patients with indolent lymphoma.
Findings
The trial confirmed equivalence of the two drugs for the primary endpoint. After a 4-week treatment period, the overall response rate in BCD-020 and rituximab groups was 45% and 42%, respectively – a statistically non-significant difference. The two drugs were associated with comparable rates of complete remission, partial remission, and stable disease. Progressive disease was noted in 8% in the BCD-020 group and 15% in the reference group. Adverse events, immunogenicity, pharmacokinetics, and pharmacodynamics findings (the latter as suggested by dramatic reductions of blood CD20+ cell counts) were similar in both groups.
The novel biosimilar BCD-020 exerts comparable overall response rates and an equal safety profile to reference rituximab in patients with indolent lymphoma. There were no substantial differences between study drug and comparator in all test parameters indicative of efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics. Considering the significant role of rituximab in the treatment of B-cell cancers and affordability of biosimilars, the incorporation of rituximab biosimilar into clinical practice may have tremendous positive benefits.
Key takeaway
Rituximab biosimilar BCD-020 has analogous molecular structure and quality characteristics to reference rituximab. In a recent study, BCD-020 had comparable overall response rates and similar safety profiles to reference rituximab in patients with indolent lymphoma.
Since the approval of two rituximab biosimilars in 2017, use of these medicines in patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL) has increased sevenfold in Germany – suggesting advanced familiarity among physicians may lessen conservative attitudes to their clinical application.
Rituximab was the first approved therapeutic monoclonal antibody in oncology and is still a fundamental component of treatment for NHL and CLL. Based on totality of evidence from a comprehensive comparability exercise, including analytical, preclinical, and clinical testing versus reference medicine, two rituximab biosimilars, Rixathon® and Truxima®, were approved by the EMA in 2017. Since real-world evidence collected during routine clinical practice in varied patient populations can usefully complement clinical trials data, this study used data from electronic health records and analysed treatment patterns with rituximab biosimilars in NHL and CLL patients in office-based care centres in Germany.
Findings
A total of 38 different rituximab-containing therapeutic protocols were used in 1,241 patients. In over 7,500 total rituximab cycles, a rituximab biosimilar was used in just over half (55%). A trend for increasing use of biosimilar over reference rituximab was noted over time. Between July 2017 and June 2019, use of biosimilar rituximab rose from 12% to 83% while that for reference rituximab slipped from 53% to 16% for both NHL and CLL. Among 70 patients who switched rituximab medicines during the observation period: approximately 50% switched from reference to biosimilar, 20% between biosimilars, and less than 30% from biosimilar to reference rituximab.
Although reasons for the selection of rituximab reference or biosimilar product were not recorded, it could be surmised that prospect of cost savings was primary motivation. Indeed, given the high cost of reference rituximab, use of its lower-priced biosimilar version could allow significant savings that might be reinvested in other aspects of healthcare. Uptake of biosimilar rituximab is increasing, likely fuelled by greater acceptance of these medicines by the oncology community combined with economic benefits.
Key takeaway
Real-world evidence collected during routine clinical practice may be used to complement clinical trials data. Analysis of treatment patterns over two years from office-based care centres showed an increasing trend for use of biosimilars over originators.
Widespread adoption of a rituximab biosimilar could have substantial positive effects both on healthcare budgets and at a societal level.
Rituximab is a monoclonal antibody that binds to CD20 protein on the surface of normal and malignant B cells, inducing their immune-mediated destruction. It is used to treat B-cell lymphomas including follicular lymphoma. Like all biologics against cancer, rituximab is associated with high treatment prices. Conversely, biosimilars are generally priced at a 20–30% discount relative to originator products, and their higher affordability implies that more patients can receive these treatments. CT-P10 (Truxima®) is the first approved biosimilar of rituximab, with identical structural and physicochemical attributes and biological activity, and licensed for the same indications. This phase III study aimed to establish the therapeutic equivalence of CT-P10 and rituximab in patients with newly diagnosed CD20-positive follicular lymphoma.
Findings
Over the 7-month observation period, an overall response was seen in 83% patients treated with CT-P10 and 81% of those receiving rituximab, suggesting therapeutic equivalence between the two groups. A similar frequency of treatment-emergent adverse events was reported for CT-P10 and rituximab – most of these were infusion-related reactions. There were no new, unexpected safety findings.
Biosimilar CT-P10 exerts therapeutic equivalence to rituximab in patients with follicular lymphoma. With one budget impact analysis suggesting the introduction of rituximab biosimilar may save healthcare systems in the EU up to €150 million per annum, the availability of CT-P10 is expected greatly to improve patient access to this revolutionary treatment.
Key takeaway
Biosimilar CT-P10 exerts therapeutic equivalence to rituximab in patients with follicular lymphoma. With one budget impact analysis suggesting the introduction of rituximab biosimilar may save healthcare systems in the EU up to €150 million per annum,the availability of CT-P10 is expected greatly to improve patient access to this revolutionary treatment.
Haematopoietic cell transplantation (HCT) is an expensive modality and developing a transplant program is especially challenging in developing countries.
For oncology and haematology patients, including those requiring haematopoietic cell transplant (HCT), high medication-related expenses (related largely to antibiotics and growth factor-type biologics), are known to hinder access to healthcare worldwide. Patent expiration for biologics may result in biosimilars entering drugs markets and thereby helping to reduce the high costs associated with these therapies.
Biosimilars are chemically similar versions of reference biologic products with no clinically significant differences. Their regulatory approval is granted based on analytical validation studies and preclinical and clinical trials, usually involving a phase III randomised comparator study versus the originator biologic.
The Worldwide Network for Blood and Marrow Transplantation (WBMT) has reported that, despite having among the highest recent increases in HCT activity, only 2% of transplant teams operate in lower-income countries such as in the Eastern Mediterranean and African regions. Latin America has a 20–40-fold lower frequency of HCT compared with Europe and North America, and this limitation is probably due to limited funding. These findings underline an urgent need to implement effective strategies to cut costs for HCT in countries with restricted resources.
Biosimilars used in the field of HCT include granulocyte colony-stimulating factors (G-CSF) for stem cell mobilization, rituximab for graft-versus-host disease (GVHD), and, possibly, infliximab and etanercept in paediatric GVHD. In a meta-analysis of reported studies, most showed no significant difference in efficacy between biosimilar and originator biologic, and where cost analysis was included, reductions were noted for biosimilars.
Key takeaway
Biosimilars have been shown to substantially reduce costs in developing countries. By 2024, the use of biosimilar G-CSFs and anti-neoplastics is predicted to result in a 10% cost reduction. The bulk of responsibility for raising awareness of biosimilars lies with governments, regulatory bodies, and local societies. Focusing on the benefits of biosimilars is an important aim for professional organisations specializing in HCT, especially for the education of practitioners in low-income countries.