Controversy of the Day Biosimilars and bioequivalents: A wise choice in a demanding treatment landscape?

Escalating costs of cancer care have led to a substantial and growing burden on healthcare systems and patients. Consequently, there is a need for biosimilars created after patent expiry of the originator agent.

Jan Schellens, Netherlands Cancer Institute

Jan Schellens, Netherlands Cancer Institute

Escalating costs of cancer care have led to a substantial and growing burden on healthcare systems and patients.1 Consequently, there is a need for biosimilars created after patent expiry of the originator agent.

Two studies of trastuzumab biosimilars for the treatment of patients with HER2-positive metastatic breast cancer were presented yesterday. Dr Hope Rugo (UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA; Abstract LBA16) described how the biosimilar, Myl-1401O, was associated with an equivalent overall response rate (ORR) to trastuzumab at 24 weeks (primary endpoint; 69.6% Myl-1401O versus 64.0% trastuzumab). Other endpoints from this phase III study in 458 randomised patients, such as progression-free and overall survival, also showed no significant difference between the agents. Importantly, safety, pharmacokinetic and immunogenicity findings appeared similar.

A second study presented by Dr Cristina Saura based on a poster by Dr Maria Shustova (JSC “BIOCAD”, St Petersburg, Russian Federation; Abstract 224PD) reported how the biosimilar BCD-022 and trastuzumab were statistically equivalent in terms of ORR (53.6% versus 53.7%, respectively), with BCD-022 showing non-inferiority to trastuzumab. Other efficacy parameters (complete and partial responses, stable disease and disease progression) were equivalent between the agents, too. Both medications were associated with comparable safety and immunogenicity findings.

While biosimilars have been available in Europe for more than a decade, they have not been universally accepted and their use varies greatly by product and country.2 In the Netherlands, for example, adoption of biosimilars has been good and estimated at 40%. However, concerns have been raised over the post-marketing quality and long-term safety of biosimilars.3 Particular concerns relate to extrapolation of indication. If the reference product is licensed to treat multiple therapeutic indications, extrapolation of the biosimilar for use in these same indications may be possible without the need for comparative clinical trials, but this must be scientifically justified.

The European Medicines Agency (EMA) has created guidelines for obtaining marketing authorisation of biosimilars.4 Regulatory approval requires that a biosimilar is characterised analytically and clinically; efficacy and safety (including immunogenicity) should be assessed in the most sensitive patient populations with endpoints that can detect any clinically meaningful differences between the proposed biosimilar and the reference product. This enables manufacturers to develop biological therapies that are broadly accessible within a tailored development programme.

1. Zelenetz AD. Oncology & Hematology Review 2016;12:22–8
2. Siegel JF, Fischer A. www.biologicsblog.com/blog/ten-years-of-biosimilars-in-europe/, 8 December 2015
3. Gascon P. Ther Adv Hematol 2015;6:267–81
4. European Medicines Agency. www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000408.jsp

This article appeared in the Monday edition of the Daily Reporter