Biologics such as rituximab and the TNF-alpha inhibitors (e.g. adalimumab, etanercept, and infliximab) have revolutionized rheumatoid arthritis (RA) care, significantly brightening the outlook for the global population affected by this potentially crippling condition. The high cost of biologics currently puts them beyond the reach of many eligible patients – but, as some frontline biologics start to approach patent expiry, new manufacturers are able to begin developing less costly versions known as biosimilars. For regulatory approval, biosimilars need to demonstrate comparable safety and efficacy to the originator biologic in a head-to-head clinical trial.
Biologics such as rituximab and the TNF-alpha inhibitors (e.g. adalimumab, etanercept and infliximab) have revolutionized RA care.4 Fifteen years ago, patients for whom conventional disease-modifying anti-rheumatic drug (DMARD) therapy was inadequate could face a bleak future.5 For many, management was a balancing act between the consequences of poorly controlled disease and the negative effects of long-term corticosteroid use.5 The development of effective and well-tolerated biologic DMARDs has dramatically improved the overall prognostic picture in RA and made remission a realistic goal.5 In addition, mounting clinical evidence shows that combination treatment with methotrexate (MTX) and a biologic DMARD is superior to MTX alone, not only in MTX-treated patients but also in treatment-naïve patients.5 And highly anticipated studies are underway to confirm the exciting finding that patients with RA who have achieved remission after early biologic treatment are able to sustain this after dose reduction and even complete cessation of the biologic prescribed.6,7
However, the reality is that many patients with RA are not able to reap the benefits of biologics. The reason, of course, is cost. In some developing nations, where healthcare focuses on fatal diseases, biologic DMARDs may be out of reach for virtually the entire population.8 Even in developed nations large discrepancies in patient access to biologics exist. In some countries, funding is generally made available but in others the cost of biologic DMARDs is often unsustainable, with many patients denied them. For example, in more than 50% of European countries, the annual cost of a biologic DMARD can exceed the per capita gross domestic product (GDP) by as much as 11 times, meaning that almost 40% of the total European population has severely restricted access to biologic DMARDs.9 In the USA, a 2014 survey of more than 100 US rheumatologists found that over 80 percent encounter moderate-to-strong control by payers when prescribing biologics for RA.10 Improving patient access to these innovative therapies is clearly an urgent priority.
The costs of modern RA biologics reflect the scientific innovation and the investment required to support biotechnological research and development. But it puts the treatments beyond the reach of many people. Pursuit of innovative new drugs is clearly of great importance, but so is broadening patient access to the treatments we have now.
There’s no quick-fix solution – but, as some frontline RA biologics start to approach patent expiry, the opportunity arises for new manufacturers to develop less costly versions, which are most commonly known as biosimilars.* Biosimilar versions of infliximab have already been approved in several regions including the EU, US, Australia, Canada, and Japan. Two etanercept biosimilars have been approved in South Korea, and one of these was approved in the EU in January 2016. Evaluation of biosimilar candidates for adalimumab and rituximab is also in progress.
*also known as follow-on biologics, subsequent-entry biologics and biocomparables, among others.
Unlike the generics of the chemical drug world, biosimilars are not exact copies of originator biologics, as it is not possible for a new manufacturer to precisely replicate the highly complex and sophisticated production processes. However, extensive regulatory requirements are designed to ensure that candidate biosimilars must be rigorously compared with their originators both analytically and clinically, to establish that quality, efficacy, and safety are all a very close match. By January 2016, 22 biosimilars in a range of therapy areas had been launched in Europe with no adverse clinical consequences compared with their originators15,16 – and have resulted in significant cost savings.17
The extent of the testing required means that biosimilars can’t be as heavily discounted as chemical generics. The average savings are projected to be 20–30%,18 but they could well be higher. For a biologic DMARD, which typically costs USD $10,000 to $30,000 per patient per year,19,20 these savings are highly worthwhile, especially as some patients may require treatment for more than a decade.21 In addition, the introduction of competition may prompt the manufacturers of originator biologics to reduce their prices and to consider investing in innovative new products as they seek new competitive advantages.
QuintilesIMS is actively supporting the development of biosimilars for RA and we invite you to join us as a clinical investigator. The patients you enroll in these studies will all receive active therapy, either with a branded biologic or a biosimilar candidate at no cost to them or to their insurers. Even if you perceive that patient access to biologics for RA is not a critical issue in your own country, getting involved in biosimilar clinical trials will give you the opportunity to help maintain the high standards required for biosimilar studies, gain experience in an area of research projected to expand significantly, and be part of a global mission to bring the benefits of modern RA treatment to a far wider population.