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.
Anaemia is a common complication of chemotherapy in cancer patients. Biosimilar epoetins can restore haemoglobin (Hb) levels, reduce fatigue, and alleviate the necessity of blood transfusions for these individuals.
Chemotherapy-induced anaemia (CIA) is an undesirable consequence of myelosuppressive chemotherapy across a large range of cancer types and is independently associated with reduced survival. However, supportive therapy leading to a successful increase in Hb response can alleviate fatigue and improve quality of life (QoL) in patients with CIA. Erythropoiesis-stimulating agents (ESAs) such as epoetins are biologics used for a sustained correction of anaemia and the resultant improvement in QoL. This real-world, observational, post-marketing surveillance study aimed to observe Hb response/normalisation in CIA patients with solid tumours, lymphoma, or myeloma treated with once-weekly subcutaneous doses of biosimilar epoetin.
Findings
Among 2333 patients enrolled at over 200 participating centres, more than 80% of patients responded within 3 months of starting epoetin biosimilar therapy and nearly 90% of patients responded within 6 months of starting treatment. Similar results were observed for patients with solid tumours, including breast and lung cancer and hematologic malignancies. In responders, the mean time to achievement of target Hb was 80 days. Overall, 17% of patients experienced at least one adverse event, including rare cases of thromboembolism. Antithrombotic agents were required by 12% of patients. No unexpected treatment-related adverse events were identified.
Although ESA biosimilars are known to provide cost-efficiency in the management of CIA, physicians should not be obliged to prescribe biosimilar epoetin for purely cost reasons. This observational study under clinical conditions adds to the body of evidence supporting the safety and efficacy of biosimilar ESA epoetin in patients with CIA.
Key takeaway
Epoetin biosimilars have facilitated an increase in many patients’ QoL via an increase in levels of Hb within 3-6 months of starting therapy. This observational study, conducted under clinical conditions, supports the safety and efficacy of epoetin biosimilar prescription.
Abstract published: August 2021
Bioequivalence of biosimilars with their reference biologic must be demonstrated by exhaustive clinical testing as mandated by regulatory authorities. As part of this process, this study assessed the comparability of a bevacizumab biosimilar versus its originator in terms of PK values using a validated computer software model.
Bevacizumab is a recombinant monoclonal antibody that inhibits angiogenesis – the formation of new blood vessels necessary for tumor growth and survival – and used in the treatment of several cancers, including non-small cell lung cancer (NSCLC). Following the release of bevacizumab originator product, PF-06439535 (ZibarevTM) is a bevacizumab biosimilar that has undergone an extensive development program of analytical, preclinical, and clinical studies.
In clinical use, bevacizumab is dosed according to body weight and intravenously infused at a constant rate. Thereafter, this antibody drug is distributed systemically to body compartments, exerts its therapeutic effects, and is eliminated metabolically by enzymatic breakdown and excretion. These processes are represented by two pharmacokinetic (PK) parameters, the drug clearance (CL) and volume of distribution (V1), which, for two biosimilar drugs, should have the same values.
Potential differences in PK between bevacizumab biosimilar and reference bevacizumab emerging from a comprehensive comparator study were investigated using a population modeling approach. In this randomized clinical trial, patients with NSCLC were treated with either PF-06439535 or bevacizumab sourced from the European Union (bevacizumab-EU), both with four to six cycles of concomitant chemotherapy, and followed for 1 year. Before and after each cycle, serum samples were collected for analysis of bevacizumab (PF-06439535 or bevacizumab-EU) concentrations by ELISA. The data were pooled and analyzed by validated population PK model using customized computer software.
In general, the model successfully reproduced the observed longitudinal bevacizumab concentration–time profiles for the entire patient pool. The model confirmed there were no appreciable differences in CL and V1 between PF-06439535 and bevacizumab-EU in patients with NSCLC. These findings provide additional support for the demonstration of PK similarity between biosimilar PF-06439535 and reference bevacizumab.
Key takeaway
The bevacizumab biosimilar, PF-06439535, demonstrated no clinical differences in either drug clearance or volume of distribution when compared with the reference product.