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Optimising anti-TNF treatment using biosimilars

Biosimilars in Clinical Practice

Read time: 15 mins
Last updated:10th Oct 2022
Published:7th Aug 2020

Biosimilars in Clinical Practice - What are Biosimilars?

Learn about biosimilar medicines, and how they can benefit the clinical management of diseases and conditions

  • Compare similarities and differences in the development processes for originator biologics versus biosimilars
  • Review anti-tumour necrosis factor (αTNF) health economic data for gastroenterology, rheumatology, and dermatology diseases
  • Learn the scientific evidence behind biosimilar development and the biosimilar regulatory approval pathway

Biological medicines have revolutionised healthcare since their development in the 1980s. Recently, biosimilars have established their place in the clinic, benefitting almost every stakeholder in the healthcare system. So, what are biosimilars and how could they be important to your practice?

A biosimilar is a medicine containing a version of the active substance of an approved biological medicine whose patent has expired (known as a reference product). A biosimilar is approved once it has been shown not to have any clinically meaningful differences in terms of quality, safety and efficacy from the reference product1,2.

As of 1 September 2022, 86 biosimilars have been approved by the European Medicines Agency (EMA)1 and 38 by the US Food and Drug Administration (FDA)3. Biosimilars based on tumour necrosis factor alpha inhibitors (anti-TNFs), such as adalimumab, etanercept, infliximab and rituximab, have been approved for the treatment of gastrointestinal, rheumatological, and dermatological diseases1,3. Anti-TNF biosimilars offer a lower cost treatment option and can potentially improve patient outcomes by providing more treatment options4.  The arrival of biosimilars has led to cost reductions that allow earlier access to effective treatments, leading to improved patient outcomes and quality of life (QoL)4. For example, the development of biosimilars to anti-TNFs such as etanercept and adalimumab for the treatment of psoriasis has led to significant improvements in health-related quality of life in patients5.

As biologic medicines, biosimilars differ from generics in their molecular size, structure and the complexity of their development1,6. Also, biosimilars are more costly and difficult to produce than generic versions of small-molecule drugs (Figure 1). It can take 5–10 years and an investment of $100–250 million to bring a biosimilar to market, compared with about 2 years and $1–10 million to develop a conventional generic6.

Biogen_Biosimilars_Bucket1_Fig1__5E1BFCE1-58C9-47E9-BC7C8029FC1E8AE5.png

Figure 1. Biological molecules have more complex structures than small molecule medicines. Mab, monoclonal antibody.

The manufacturer of an original biological medicine must demonstrate its safety and efficacy in clinical trials. Biosimilar development focuses on in-depth analyses to confirm that the biosimilar is highly similar to its reference product in terms of structure, composition, and in vitro activity1. At least one clinical study is required to compare the pharmacokinetics of the reference product and biosimilar, and at least one randomised trial is required to demonstrate clinical equivalence (Figure 2)1,7.

 

Biogen_Biosimilars_Bucket1_Fig2__B614B1C5-5EBC-4C7C-A42F0E73491CD59D.png

Figure 2. Drug development comparison. The development processes for biologics and biosimilars are considerably more rigorous than the development process for small molecule generics (Adapted8). PD, pharmacodynamics; PK, pharmacokinetics.

If a biosimilar has comparable safety and efficacy in one therapeutic indication to a reference product, then the data may be extrapolated to other indications already approved for the reference medicine7,9. Consequently, a biosimilar may be approved in all indications for which the reference product has been approved without multiple clinical trials7. Safety data are monitored and reported on a continuous basis according to rigorous pharmacovigilance regulations outlined by the EMA and US FDA1,9.12,13

Interchangeability can have a scientific or legal meaning10:

  • In the EU, interchangeability is a scientific term meaning that a product can be safely switched 
  • In the US, it is a legal term which allows automatic substitution at the pharmacy level 

Interchangeability is slightly different to 'switching', which refers to the treatment decision made by a physician to switch patients treated with a reference product to a biosimilar. Substitution refers to a pharmacist substituting one prescribed reference product for a biosimilar without the need to consult a physician1.

It is estimated that in the UK, the healthcare system can make substantial savings of £200–300 million per year if patients are initiated on or switched to biosimilars11. These savings can then be reinvested into other aspects of patient care to increase the number of health service staff, to increase funding for nurses and to maintain the quality of the social care system11. As the number of treatment options increases, manufacturers reduce the prices of their products to increase market share and this in turn increases patient access to biologic medicines (Figure 3)12,13.

Biogen_Biosimilars_Bucket1_Fig3__15FB6660-E1E7-4800-BDF4DFA022FD218E.png

Figure 3. Estimated cost savings in the US by biologic class, 2017–2026 (Adapted12). Anti-TNF, anti-tumour necrosis factor; COPD, chronic obstructive pulmonary disease.

The Health Economic Perspective

In this short video, Professor Thomas Dörner (Charité University Hospitals, Berlin, Germany) describes how the arrival of anti-tumour necrosis factor (TNF) biosimilars has affected access to biologic treatment options, the initiation of treatment, and how various countries, including South Korea, Australia and European nations, have expanded their use of anti-TNF biosimilars.

Professor Thomas Dörner (Charité University Hospitals, Berlin, Germany) asks if the use of biosimilars is associated with stigma. Learn about the need for greater education in biologics and biosimilars, such as their validation processes and biomarkers.

Biosimilars provide benefits from a health economics perspective11,13. But do anti-TNF biosimilars offer value across gastrointestinal, rheumatological, and dermatological diseases?

Inflammatory bowel disease

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How can patients use biosimilars, and what evidence supports their use?

In this short video, Professor Joao Gonclaves (Director, iMed-Research Institute for Medicines; Professor of Immunology and Pharmacology, University of Lisbon, Portugal) introduces the assessment of biosimilars, and biosimilar safety, efficacy, and tolerability data.

Professor Joao Goncalves (Director, iMed-Research Institute for Medicines; Professor of Immunology and Pharmacology, University of Lisbon, Portugal ) outlines how education on biosimilars should include the mechanisms of action of biologics, how to mitigate the nocebo effect, and the need for support programs for patients and healthcare professionals.

Recently the concept of the nocebo effect has gained renewed interest as a result of introducing biosimilars in therapy. Nocebo effects are negative responses to a therapeutic agent that cannot be explained by the pharmacological properties of the agent28. Various factors that give rise to negative expectations of a treatment, including psychological, physiological and neurobiological factrs, can contribute to nocebo effects28,29. In the case of biosimilars, gaps in patient and healthcare professional (HCP) awareness, understanding and perception may contribute to the nocebo effect, reducing the clinical benefit of biosimilars28.  In some cases, patients have discontinued biosimilars, despite having no worsening of disease, after switching from reference products28

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Welcome:

References - Biosimilars in Clinical Practice

  1. European medicines Agency. Biosimilar medicines: overview. https://www.ema.europa.eu/en/human-regulatory/overview/biosimilar-medicines-overview#information-for-patients-and-healthcare-professionals-section. Accessed 20 September 2022.
  2. European Medicines Agency and the European Commission. Biosimilars in the EU - Information guide for healthcare professionals. 2019. Available at: https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf. Accessed 19 April 2022.
  3. FDA. Biosimilar Product Information | FDA. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information.
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