Trastuzumab, the first of the HER2-directed therapies, has dramatically improved outcomes for patients with HER2-positive breast cancer and is seen as one of the major success stories in modern oncology. The high cost of trastuzumab currently puts it beyond the reach of many eligible patients – but, as its patent expiry approaches, 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.
Breast cancer is the most commonly diagnosed cancer in women worldwide. Despite preventative measures and screening programs, it is also the most common cause of cancer mortality.1 In 2012 alone, there were 1.7 million new cases of breast cancer and over half a million deaths from breast cancer worldwide.1 What’s more, breast cancer is on the rise1 and seems set to remain one of the top causes of female cancer deaths for at least another 15 years.2
The ability to identify and target HER2-positive breast cancer, which accounts for 20–25% of all cases, was a major breakthrough in breast cancer management.3 Trastuzumab, the first of the HER2-directed therapies, has dramatically improved outcomes for patients with early* or metastatic disease.† It is currently considered standard of care6 and is recommended by clinical guidelines worldwide, including those in Europe and the USA.7,8 And although research into HER2-targeted intervention has rapidly expanded the range of therapeutic options available, trastuzumab remains a central component of most HER2-directed treatment strategies.9,10
* Overall survival at 10 years: 84.0% vs 75.2%; 37% reduction in risk (trastuzumab plus chemo vs chemo alone)4
† Median time to disease progression: 7.4 months vs 4.6 months (trastuzumab plus chemo vs chemo alone)5
Unfortunately, many of the world’s cancer patients are not able to reap the benefits of modern research. The reason, of course, is cost. In some developing nations – where a course of trastuzumab can cost more than ten times the average annual wage11 – cancer biologics may be out of reach for virtually the entire population. Even in developed nations, large discrepancies in patient access to biologics exist. For example, clinical oncologists surveyed in Europe and America frequently cite cost as a barrier to prescribing trastuzumab.12 This cost is in addition to that of chemotherapeutics given in combination with trastuzumab,13 as well as the cost of preventing or managing neutropenia secondary to chemotherapy.14 More recently, this cost has risen even further with the approval of another monoclonal antibody, pertuzumab.15,16 For those patients who opt to self-fund, it’s easy to see how a cancer diagnosis can wipe out entire life savings, especially as the costs are often incurred at a time when earning a living may be impossible.17
The cost of modern cancer biologics reflects the scientific innovation and the investment required to support biotechnological research and development. But it puts these 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 modern cancer biologics start to approach patent expiry, the opportunity arises for new manufacturers to develop less costly versions of them which are most commonly known as biosimilars.‡ A trastuzumab biosimilar has already been approved in South Korea and plans are in place to launch several more in other countries as soon as possible after expiry of the originator drug patent.22
‡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 originators23,24 – and have resulted in significant cost savings.25
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%,26 but they could well be higher. For a biologic that can cost up to USD $100,00027 per patient per year, these savings are highly worthwhile. Biosimilars have already helped increase patient access to essential biologics: in the UK, for example, more physicians are now able to provide cancer patients with granulocyte colony stimulating factor (G-CSF) medication to ward off neutropenia at an early stage.28 In addition, the introduction of competition might 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 breast cancer 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 the branded biologic or a biosimilar candidate at no cost to them or to their insurers. Even if you perceive that patient access to trastuzumab 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 breast cancer treatment to a far wider population.