Fast Facts: Biosimilars in Hematology and Oncology

Biologics and biosimilars - getting decisions right

P. Cornes, A. McBride, Paul Cornes, Ali McBride

• Publisher: S. Karger
• Year: 2020
• Print ISBN: 9781912776214
• eBook ISBN: 9781912776221
• Topic: Medicine
• Subtopic: Oncology

Biologics have revolutionized – and are revolutionizing – the treatment of many serious disorders. The evidence acquired from more than 10 years of clinical experience, with more than 50 biosimilar drugs and more than 700 million patient-days' exposure in Europe, shows that approved biosimilars can be used as safely and effectively as originator biologics. Yet concerns persist about biosimilars – particularly in curative cancer treatment, where they are relatively recent therapeutic options. 'Fast Facts: Biosimilars in Hematology and Oncology' provides a concise overview of emerging global practice in this fast-moving area together with practical information on adding biosimilars to a formulary and switching patients.

1	Biologics and the need for biosimilars

Biological medicines (biologics) are drugs derived or extracted from living systems, usually modified bacteria, fungi or animal cells; the three main categories are listed in Table 1.1. Biologics have been able to transform the outcomes of many previously hard-to-treat diseases, becoming an essential component in the treatment of diseases including diabetes, anemia, rheumatoid arthritis and cancer. This is reflected in the inclusion of biologics in the WHO list of essential medicines. These ‘essential medicines’ are those the WHO believes should be provided free, or at prices all citizens can afford; but this creates a problem. Biologics are inherently more expensive than past-generation medicines; they represent the result of costly investment in research and development and are manufactured using cellular-based technologies and utilizing gene expression. The combination of medical benefit but high costs for biologics creates the need for biosimilars.

TABLE 1.1

Three main categories of biologics (many with importance in hematology and oncology)

Category	Examples
Products that are almost identical to natural products the body makes – often used as replacement therapy or to augment the body’s own response	•Filgrastim •Epoetin •Human growth hormone •Human insulin •Follitropin
Monoclonal antibodies that bind to soluble or cell-surface proteins and block pathways or cells	•Trastuzumab •Rituximab •Bevacizumab
Engineered proteins that mimic receptors (soluble receptors or receptor antagonists), but are soluble and designed to be stable in humans	•Infliximab •Adalimumab •Etanercept

Costs and economics

The transition from the era of small molecule drugs to that of the biologics has markedly increased drug expenditure – and especially so for cancer. For example, 8 weeks of standard chemotherapy for advanced colorectal cancer cost US$63 in the small molecule era but $30 790 using biologics, representing an almost 500-fold increase in drug costs – although this has been accompanied by improved outcomes.¹ The high prices of biologics are justified by manufacturers on the basis of the investment in discovery, development and production.

Biological agents represent the largest growth in pharmaceutical innovation, with new agents submitted for approval annually. In 2017, for example, more than 200 molecules were in late-stage development for cancer and hematologic malignancies – up over 60% from a decade ago. Almost 90% of those therapies in development were targeted biological treatments.²

The current cost of biologics is rising quickly – threatening the sustainability of healthcare.³ So significant is this threat to delivering global cancer treatment that the WHO 70th World Health Assembly of 2017 established a Technical Working Party to report on the impact of drug pricing in cancer.⁴ The WHO report noted that, in relative terms, prices and costs of cancer medicines are higher than the prices and costs of medicines used in other therapeutic areas; over 1997–2016, the median annual cost of monoclonal antibodies was significantly higher when used in oncology and hematology (US$142 833) compared with the next highest-priced therapeutic categories: immunology (US$53 969); infectious disease; and allergy.

The result has been problems with access to innovative medicines. Access to biological drugs, whether anti-inflammatory or cancer, is strongly associated with national wealth.^5,6

There is a consensus on solutions; health systems need to maximize the use of competition between manufacturers to check prices. For this to work, nations need to encourage the early launch and swift uptake of competitor medicines once patents have expired.⁷ For conventional synthetic small molecule medicines, these competing brands are called generic medicines, while the follow-on versions of biologics are termed biosimilar medicines (in countries including Europe, USA and Japan) – see Table 1.2 for definitions.

TABLE 1.2

Key definitions: generics and biosimilars

Biological medicinal product (biologic [reference/originator])	•Medicinal product in which the active substance is made by or derived from a living organism
Biosimilar medicinal product (biosimilar)	•Similar to a biologic that has already been authorized (the reference product) •The active substance is highly similar to that of the reference biologic, notwithstanding the natural variability inherent to all biologics (see page 17) •The name, appearance and packaging of the biosimilar may differ from those of the reference biologic, and the biosimilar may contain different inactive ingredients •The drug has been regulated following the stepwise comparability procedures of the biosimilar regulatory pathway pioneered by the European medicines regulator and subsequently adopted by agencies such as the US regulator and WHO •The premise of a biosimilar is that there are no clinically meaningful differences between it and the reference medicine in terms of safety, quality and efficacy
Generic medicinal product (generic)	•In contrast to a biosimilar, a traditional generic medicine has the same qualitative and quantitative composition of active substances and the same pharmaceutical form as the reference medicinal product •A generic may differ in characteristics such as manufacturing process, formulation, excipients, color, taste and packaging •Bioequivalence with the reference medicinal product is demonstrated by appropriate bioavailability studies – usually as a head-to-head p...

Table of contents

• Cover
• Title Page
• Copyright
• Contents
• Glossary
• Introduction
• 1 Biologics and the need for biosimilars
• 2 Why do we need biosimilars?
• 3 How is the quality of biosimilar medicines assured?
• 4 Legal issues
• 5 Switching, interchangeability and extrapolation
• 6 Safety and pharmacovigilance
• 7 Global issues
• 8 Formulary considerations: pharmacy issues
• 9 Formulary considerations: supportive care biosimilars
• 10 Formulary considerations: therapeutic anti-cancer biosimilars
• 11 Communication and awareness
• Useful resources
• Index