Type: Formulary

Abstract published: August 2021

Development of a standardised approach for evaluating and assimilating biosimilars should improve efficiency of their integration into existing workflows. A comprehensive cancer centre shares some practical considerations to serve as a guide to other institutions as they navigate the biosimilars landscape and support the transition to biosimilars in practice.

Biosimilars – biological products that are highly similar to reference products with no clinically meaningful differences – were allowed to enter the US market following ratification of the Biologics Price Competition and Innovation Act. Access to these potentially cheaper drugs was anticipated to reduce total pharmaceutical expenditures in the USA ranging between $24 and $150 billion within a 10-year period, with a corresponding reduction in total spending on biologics of approximately 3%. However, biosimilars still comprise less than one third of the total biologics use.

For cancer patients, providers seem more amenable to use biosimilars in the settings of palliation and supportive care than for curative purposes. Barriers to more widespread use of oncology biosimilars may include prescribers’ concerns over safety and efficacy, pricing and contract issues, and laws and regulations for substitution and interchangeability. These barriers may be effectively overcome by better prescriber education on switching studies, clear FDA guidance on substitution, and reform of formulary policies. And from a practical standpoint, willingness to provide temporal and financial investment to operationalize transition to biosimilars is required.

For the above reasons, a comprehensive cancer centre in Houston, TX reports the strategies, challenges, and lessons learned when they elected to move forward with biosimilars.

The first biosimilar evaluated for formulary addition at the cancer centre was the hematopoietic growth factor filgrastim-sndz. After a failed preliminary assessment, subsequent payer policy change and greater opportunities for cost savings, coinciding with publication of post-marketing safety data, led to re-evaluation and full implementation of the biosimilar alongside formulary deletion of the reference biologic. Formulary review for this process included the following steps – first, cost, coverage, and access were evaluated, followed by formulary preparation for use of the biosimilar with engagement of requesting physician, pharmacy, and therapeutics (P&T) committee, and purchasing personnel.

These experiences allowed the cancer centre to transition to biosimilar implementation within an effective timeline.

Key takeaway

Trastuzumab is the gold standard of treatment for HER2-expressing cancers, although it is associated with an iThere are many barriers to the increased use of oncology biosimilars in treatment: concerns over safety and efficacy, pricing and contract issues, and laws and regulations for substitution and interchangeability. Improved prescriber education on switching studies, clear FDA guidance on substitution, and reform of formulary policies may help to overcome these barriers and start the transition to biosimilar implementation.

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.

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.