For patients with metastatic colorectal cancer (mCRC), the anti-angiogenic biologic bevacizumab can sometimes make a significant clinical difference when added to chemotherapy, including improvements in overall survival. The high cost of bevacizumab currently puts it beyond the reach of many eligible patients – but, as its patent expiration approaches, new manufacturers are able to begin developing less costly versions, known as biosimilars. For regulatory approval, biosimilars need to demonstrate similar safety and efficacy to the originator biologic in a head-to-head clinical trial.
Colorectal cancer (CRC) is the world’s fourth most common cancer.1 New CRC cases are estimated to exceed 1.2 million worldwide, with more than 600,000 deaths annually. Despite improvements in screening, approximately 20% of patients with CRC already have metastatic disease at the time of diagnosis. In addition, many of those diagnosed at an early stage eventually develop metastases, resulting in an overall mortality rate of 40–45%.2
Alongside standard chemotherapy, the introduction of targeted biologics has substantially broadened the treatment options for metastatic colorectal cancer (mCRC).2 For example, bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) – an essential regulator of angiogenesis – has been shown to prolong overall survival (OS) and progression-free survival (PFS) when added to chemotherapy for mCRC.3
When 5-fluorouracil (5-FU) and leucovorin were the only therapeutic options, the OS for patients with mCRC was between 10 and 12 months; this was extended to 18 months when irinotecan or oxaliplatin were added. The use of targeted biologics such as cetuximab and bevacizumab has been shown to delay disease progression and prolong OS by a few more months. For cetuximab the benefit has been shown to depend on specific mutation status, while this remains unclear for bevacizumab.4 Identifying better predictive biomarkers for patients most likely to respond should enable more selective use of these agents, which can make a significant difference in some individuals.5
In the meantime, many patients with cancer are not able to reap the benefits of modern research. The reason, of course, is cost. Around the world, healthcare authorities and insurers are declining to fund cutting-edge cancer therapies because of their high price tags – and patients who decide to self-fund are frequently faced with a significant financial burden and even bankruptcy.6–8 In some developing countries, cancer biologics may be out of reach for virtually the entire population. Even in Western countries, large discrepancies in patient access to biologics exist.9,10
The UK’s National Institute for Health and Care Excellence (NICE) has repeatedly declined to fund bevacizumab on the National Health Service (NHS) for eligible patients with CRC, as well as other licensed indications such as non-small cell lung cancer (NSCLC) and ovarian cancer.11 Similarly, in the USA, bevacizumab is prescribed by oncologists for many cancer types but its cost remains a barrier to patient access.12 A recent survey of US managed care organizations (MCOs) indicated that two-thirds would lower co-insurance charges for bevacizumab if it were less expensive.13“Scientific advancement in cancer treatment has unfortunately led us into a quagmire of uncontrolled cost and healthcare expenditures. Cancer care expenditures are projected to reach $173 billion in the US by 2020. To put this into perspective, NASA spent $2.5 billion to send rover ‘Curiosity’ to Mars, and the cost of the ﬁrst human mission to Mars is estimated to cost around $100 billion. The prices of patented cancer drugs have increased from $10,000 per year to $100,000 per year since 2000, resulting in crippling ﬁnancial hardships and mountains of debt for average income families.” 14
The prices of novel cancer biologics reflect the scientific innovation and the investment required to support biotechnological research and development, but it puts them beyond the reach of many people. Pursuit of innovative new drugs is clearly of great importance, but so is broadening patient access to currently available treatments. There’s no quick-fix solution – but, as biologic drugs like bevacizumab start to approach patent expiration, the opportunity arises for other manufacturers to develop less costly versions of them, which are most commonly known as biosimilars.*
*Also known as follow-on biologics, subsequent entry biologics (SEBs) and biocomparables, among other terms.
Unlike the generics of the chemical drug world, biosimilars are not exact copies of originator biologics, since it is not possible for a new manufacturer to precisely replicate the highly complex and sophisticated production processes used by the originator. Therefore, extensive regulatory requirements have been implemented to ensure that candidate biosimilars are rigorously compared with their originators both analytically and clinically, to establish that quality, efficacy, and safety (including immunogenicity) are all a very close match. As of September 2016, 23 biosimilars, in a range of therapeutic areas, have been launched across Europe with no adverse clinical consequences compared with their originators15,16 – and have resulted in significant cost savings.17
The complex manufacturing process and the extent of the testing required means that biosimilars can’t be as heavily discounted as chemical generics. The average saving is projected to be 20–30%,18 but it will sometimes be higher as a result of commercial negotiations with payers and if the originator price is reduced under competitive pressure. For a biologic that can cost up to USD $100,000 for a year of treatment, these savings are highly worthwhile.7,19,20
Learn more About Biosimilars, Regulatory Requirements, and Biosimilars by Region
The high price of targeted biologics like bevacizumab restricts their accessibility, meaning that clinicians' options become more limited and patients are denied access to potentially life-prolonging drugs. Access to a range of therapeutic options is important in a condition like mCRC where the choice of alternative regimens is already limited. Only two other biologics targeting angiogenesis (ziv-aflibercept and ramucirumab) are approved for mCRC treatment and these are no more affordable than bevacizumab.21 The availability of more affordable biosimilar versions of bevacizumab can therefore be expected to help increase access to anti-angiogenic treatment for the eligible mCRC patient population.
Quintiles is actively supporting bevacizumab biosimilar trials in CRC 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 Avastin® (bevacizumab) or the biosimilar candidate, at no cost to them or their insurers. Even if you perceive that patient access to biologics like bevacizumab 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 of biosimilar studies, gain experience – with your own patients – in an area of research projected to expand significantly, and be part of a global mission to bring the benefits of modern cancer treatment to a far wider population.
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2. Hohla F, Winder T, Greil R et al. Targeted therapy in advanced metastatic colorectal cancer: current concepts and perspectives. World J Gastroenterol (2014) 20:6102–6112.
3. Kozloff M, Yood MU, Berlin J et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: The BRiTE observational cohort study. Oncologist (2009) 14:862–870.
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6. Express, 16 March 2014. The good fight: A drug that can add years to lives of ovarian cancer patients. http://www.express.co.uk/life-style/health/464835/Ovarian-cancer-drug-Avastin-can-add-years-to-lives-of-patients. Accessed 10 October 2016.
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9. National Institute for Health and Care Excellence (NICE), 22 May 2013. NICE finds advanced ovarian cancer treatment too expensive with not enough benefit. https://www.nice.org.uk/news/press-and-media/nice-finds-advanced-ovarian-cancer-treatment-too-expensive-with-not-enough-benefit. Accessed 10 October 2016.
10. News.com.au, 8 August 2014. Avastin, first new ovarian cancer treatment in 15 years, subsidised. http://www.news.com.au/lifestyle/health/avastin-first-new-ovarian-cancer-treatment-in-15-years-subsidised/story-fneuzlbd-1227017130109. Accessed 10 October 2016.
11. PMLiVE, 26 March 2013. Another NICE rejection for Roche’s Avastin. http://www.pmlive.com/pharma_news/another_nice_rejection_for_roches_avastin_469208.
12. NEWS Medical. Avastin (bevacizumab) price. http://www.news-medical.net/health/Avastin-(Bevacizumab)-Price.aspx. Accessed 10 October 2016.
13. Decision Resources, 28 September 2009. Although most surveyed oncologists prescribe it for many cancer types, Avastin’s high cost remains a barrier to treatment for some patients. https://decisionresourcesgroup.com/press-releases/123996-although-most-surveyed-oncologists-prescribe-it-for-many-cancer-types-avastins-high-cost-remains-a-barrier-to-treatment-for-some-patients/. Accessed 10 October 2016.
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18. PharmTech.com, 30 September 2014. New report details players and pipelines in the biosimilar space. http://www.pharmtech.com/pharmtech/News/New-Report-Details-Players-and-Pipelines-in-the-Bi/ArticleStandard/Article/detail/855810. Accessed 10 October 2016.
19. FiercePharma, 27 June 2014. EU backs Roche's Avastin for hard-to-treat ovarian cancer. http://www.fiercepharma.com/story/eu-backs-roches-avastin-hard-treat-ovarian-cancer/2014-06-27. Accessed 10 October 2016.
20. ScienceDaily, 1 June 2014. Ovarian cancer subtypes may predict response to bevacizumab. http://www.sciencedaily.com/releases/2014/06/140601201956.htm. Accessed 10 October 2016.
21. Goldstein DA and El-Rayes BF. Considering efficacy and cost, where does ramucirumab fit in the management of metastatic colorectal cancer? Oncologist (2015) 20:981–982.