Type: Abstract Library

A selection of evidence-based and peer-reviewed literature to expand your learnings on biosimilars and increase your confidence of their use in clinical practice

Bioequivalence confirmed in the first population PK analysis for a bevacizumab biosimilar based on a comparative clinical study in patients with cancer

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.

Improving supportive care: lessons we can learn from the introduction of biosimilars into general healthcare

Abstract published: August 2021
Several efforts have been introduced to improve access to biosimilars and deliver cost savings to healthcare systems. This review considers some of these recent initiatives.

Biosimilar use is set to increase significantly in cancer patients requiring supportive care; however, several challenges to implementing biosimilars into clinical practice remain.

Epoetin-α is an erythropoeisis-stimulating agent (ESA) that improves haemoglobin levels in patients receiving chemotherapy and reduces their need for blood transfusions. Since the first epoetin-a biosimilar was launched in Europe in 2007, many short- and long-acting biosimilar versions of this drug have been made available worldwide, with apparently similar degrees of efficacy. The introduction of biosimilar ESAs and consequent cost reductions for these drugs in the UK led the National Institute for Health and Care Excellence (NICE) to review its stance on their cost-effectiveness and subsequently to approve them for reimbursement on the NHS, in 2014. Similarly, there is now acceptance and expanded use of biosimilar versions of filgrastim across Europe and the USA.

Despite the known advantages of adopting biosimilars into oncology practice, there is a lack of confidence among prescribers. Areas where healthcare professionals report having knowledge gaps include the biosimilars approval processes, pharmacovigilance, and concepts of extrapolation and interchangeability. Patients, caregivers and the general public also may not accept biosimilars, therefore good-quality education resources for HCPs and patients alike have been made available by a number of bodies including professional societies and government organizations, along with continued gathering and dissemination of pharmacovigilance and pharmacoeconomics data.

Differences in the way biosimilars are commissioned and reimbursed can also influence uptake. Healthcare policies that incentivize competition and sustainable pricing, such as value-based care schemes, ensure manufacturers continue to invest in the biosimilars market. The UK Cancer Vanguard project provides a good example of an initiative to speed up biosimilar uptake – in this case, rituximab. This project, which included stakeholder engagement and teaching materials, financial incentives and targets for implementation, was rewarded with biosimilar infliximab achieving 90% market share within 12 months.

Clearly, to enhance access to biosimilars in supportive care, several existing barriers should be addressed. These include increased standardization of regulation, commissioning and reimbursement, better product availability and not least, clearer understanding of the broad usefulness of biosimilars.

Key takeaway

Prescribers and patients often lack knowledge about biosimilars, thus lowering their acceptance in clinical care. There are knowledge gaps in several areas (e.g., approval processes, pharmacovigilance, and extrapolation and interchangeability) which need to be addressed before take-up increases. Healthcare policies incentivising competition and sustainable pricing ensure manufacturers continue to invest in the biosimilars market.

Greater understanding of biosimilars among healthcare providers is key to driving their uptake

Abstract published: August 2021
With a wealth of therapeutic biosimilars on offer for inclusion in formularies, what are the most useful considerations on adopting them into oncology practice?

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) was passed by US Congress to provide an abbreviated approval pathway for biosimilars. Since then, a host of biosimilars have been launched and provide a broad range of options for anticancer treatment – both immunotherapies and targeted agents – and supportive care in oncology.

The total expenditure on novel biologic therapy was estimated at $68 billion in 2020. By contrast, due to their simpler and expedited approval and manufacturing processes, biosimilars are predicted to reduce the total direct cost of biologics by $54 billion over the next 10 years. This reduction will depend on several factors beyond price competition, including confidence in the use of biosimilars among the medical community and their acceptance by patients.

Biosimilar development must include analytical analyses of structure and function and clinical testing, although requisite clinical trials are reduced in number and scope compared with those stipulated for the originator biologic. Clinical similarity studies confirm there are no clinically meaningful differences between the candidate biosimilar and its originator biologic in terms of efficacy, safety, and immunogenicity. Switching studies may also demonstrate interchangeability – evidence that the biosimilar can be prescribed instead of its originator biologic without diminishing its beneficial effects. Once approved for clinical use, biosimilars are subject to strict post-marketing safety monitoring, which must include adequate mechanisms to differentiate adverse events reported for the biosimilar versus reference biologic.

Pharmacy and Therapeutics (P&T) committees must review whether the totality of evidence justifies the indications under formulary consideration. P&T committees should review all data on the sensitive population included in clinical trials of the biosimilar and assess whether they support extrapolation of its use in the intended population. It is important to consider hospital infrastructure in addition to drug acquisition cost – and whether these support full formulary conversion to the biosimilar. Finally, challenges to incorporating biosimilars into practice must be overcome, often necessitating provision of education for healthcare providers as well as patients. Pharmacists play an essential role in helping gain acceptance of biosimilars on formularies and thereby increase treatment options for people with cancer.

Key takeaway

Biosimilars must show no clinically meaningful differences between the candidate biosimilar and its originator biologic in terms of efficacy, safety, and immunogenicity, and are subject to strict post-marketing safety monitoring. Challenges to uptake of biosimilars include drug cost and infrastructure cost, as well as healthcare professional and patient education.

Comparison of regulatory, quality and clinical aspects of available LMWH biosimilars may be helpful for their selection and uptake

Abstract published: August 2021
With at least 8 branded low-molecular weight heparins (LMWH) internationally available, which LMWH biosimilar should be kept in formulary?

Although nowadays largely superseded in clinic by direct-acting oral anticoagulants, LMWH, such as enoxaparin, remain drugs of choice for cancer patients at risk of venous thromboembolism and for prophylaxis during pregnancy and are widely prescribed.

In the USA, follow-on LMWH products are considered generics, whereas in the EU they are considered biosimilars. The EMA approval process for new LMWH biosimilar applications specifies a number of non-clinical and clinical studies be conducted – the former including quality comparisons and the latter at least a pharmacodynamics study looking at anti-FXa and anti-FIIa activity (monitoring anti-coagulant therapy) and release of tissue factor pathway inhibitor (TFPI) in healthy volunteers. A dedicated comparative efficacy trial is not necessary, although safety and immunogenicity assessment in patients is mandatory. As with all approved biosimilars, a pharmacovigilance/risk management plan is required within the EMA’s authorization procedure.

Most LMWH products are prepared from porcine intestinal-derived unfractionated heparin, which is partially depolymerized to the required molecular weight. The depolymerization process can be achieved by several means – resulting in small, structural differences among the various LMWH generics/biosimilars. However, all these products are approved for the same indications.

Three biosimilarity studies for enoxaparin have been conducted, and all concluded the products were bioequivalent. Moreover, pharmacovigilance for LMWH biosimilars in the EU has not led to any safety signals.

So, which LMWH should be stocked in formularies? A group of Dutch clinical pharmacists and researchers from Queen’s University Belfast have devised a model for formulary uptake decisions termed System of Objectified Judgment Analysis (www.sojaonline.com). The model provides a system of critical weight factors for Pharmacy and Therapeutic committee voters to assess each available product, with that achieving the highest score recommended for inclusion. This system favors products with modern analytical tests for impurities, phase III clinical data, prophylactic and therapeutic dosage forms available – and an attractive price. For LMWH uptake, this model provides a straightforward, transparent process to enhance policy making.

Key takeaway

LMWH remains widely prescribed for cancer patients in need of anti-coagulation therapies. A novel System Objectified Judgement Analysis model has been released which provides a transparent policy-making process for deciding which LMWH biosimilars provide the best cost-benefit and should be stocked in pharmacy formularies.