“Cutting edge biology can be an uncertain place for patients, investors and governments. But it can also be the door to success”
In recent years, a string of successful clinical results has ignited an explosion of spending from investors and pharmaceutical executives and delivered astonishing results for many patients. The cause, immunotherapy. Arguably, no innovation since the introduction of chemotherapy in the 1940’s has had a bigger impact on the treatment of cancer than the new generation of immunotherapies has. And unarguably, no treatment has had bigger impact on the Pharmaceutical Benefits Scheme (PBS). Immunotherapy treatment isn’t new, but it is revolutionising the way we treat cancer—in more ways than one.
Cancer is the second leading cause of death in the developed world. Remarkably, modern science has dramatically increased the median survival of patients across many different cancers. While these advancements have been due to the introduction of cytotoxic agents into treatment plans thus far, a new class of drugs are improving patient outcomes in the most dramatic of ways.
By harnessing the body’s own immune system, patients can turn a fatal disease into a chronic one or even have it resolve completely. Rather than targeting tumours directly, cancer immunotherapy enlists antibodies to block receptors found on T cells, setting off a chain reaction that leads to a deadly and remarkably efficient assault on cancer cells.
In 1891, William B. Coley was the first to tap into immunotherapy when he injected streptococcal organisms into the neck tumour of an Italian man. The effect was instant, with the tumour shrinking – it was the first documented example of immunotherapy. Today, several waves of treatment types for cancer have arisen, including; radiation therapy, chemotherapy and hormonal therapy. The major type of modern immunotherapy—immune checkpoint blockade therapy—has undoubtedly been one of the most impressive advancements we’ve seen so far in terms of health outcomes.
Immunotherapy, when applied, can be extremely effective. One of the earlier (and more successful) immunotherapy drugs that has been developed and launched on the market is Ipilimumab (Yervoy), which was approved by the Therapeutic Goods Administration (TGA) in 2011. The drug, designed to treat advanced melanoma cancer, has delivered significant success to many patients, prolonging overall survival with no impact on overall response rate (10%) or progression free survival (PFS) in melanoma*.
Immunotherapy is less aggressive on a patient’s body in comparison to typical cytotoxic agents. This allows patients to have a higher quality of life during treatment; improving tolerance, compliance and reducing side effects. This is due to the nature of the therapy, kickstarting the body’s immune system to destroy cancer cells as opposed to inducing death in cells that have a high rate of proliferation. This can affect tumour and healthy cells alike, also delivering a side effect profile that is deeply challenging for many patients.
All types of cancer therapies can be used alone or in conjunction with one another. For example, immunotherapy can work synergistically with other therapies, such as chemotherapy or radiation therapy. Together, these treatments are proving to be far more effective, attacking tumours with several different, independent strategies.
As expected with a treatment revolution such as this, there is an unprecedented amount of interest in commercialising these new treatments. Investors and large pharma companies have been quick to divert funds into immunotherapy development, with Bristol-Myers currently dominating—selling near nine billion worth of therapies in the first wave of checkpoint inhibitors (since going on sale in 2015)**.
This has been quickly followed by other companies, equating to billions of dollars in sales around the world, following billions of dollars invested in the research and development of such therapies. As a result, an estimated 800 clinical trials involving a checkpoint inhibitor are currently underway in the US.
The rapid pace at which immunotherapy is evolving is putting a pressure on investors, government agencies, healthcare budgets and patients. The hype surrounding immunotherapy has given rise to an unsustainable funding/costing framework coupled with an enormously powerful pull from patients to access innovator medicines. With prices of drugs varying between $20,000 and $150,000 per treatment month, it’s a tough balancing act for government in deciding to subsidise and for patients trying to finance a return to health. These prices push the governments finite PBS funds like never before, risking making many of these treatments too expensive under the current healthcare system. If the range of immunotherapy drugs expands (which they will), Australia will have to reassess our current healthcare funding system.
Despite it being hailed as the next greatest revolution in cancer treatment, it doesn’t work for everyone—very few in fact. For example, immunotherapy has only demonstrated a clinical benefit for approximately 15 – 20% of patients with urothelial carcinoma***. Understanding the intricacies of effective tumour immunity will depend on the extensive integration of complex biological and technological innovation.
There are also significant road blocks that hamper the progress in immunotherapies both in the laboratory and clinical trials. The cost and complexity of comprehensive tissue studies and the limited availability of human tumour blood and tissue samples are an example of such issues.
The best steps we can take to propel us into the future is to take advantage of these opportunities and whilst creating strategies to overcome challenges From Coley to the release of Illipmunab, the field of immunotherapies has progressed considerably. Even though the immune system remains largely misunderstood, it’s a relief to know that progress is happening and that those with the means to advance immunotherapies are committed and well financed.
*Emens, L. (2017). Cancer Immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape. Science Direct, [online] pp.121-125. Available at: https://www.sciencedirect.com/science/article/pii/S0959804917309188 [Accessed 21 Apr. 2018].
**Molteni, M. (2017). The most promising cancer treatments in a century have arrived-but not for everyone. Wired, [online] p.1. Available at: https://www.wired.com/story/cancer immunotherapy-hasarrived-but-not-for-everyone/[Accessed 21 Apr. 2018].
***Connelly, S. (2017). Durable Immunotherapy Benefits Foster Excitement in Bladder Cancer, Despite Low Response Rates. Targeted Oncology, [online] Available at: http://www.targetedonc.com/news/durable-immunotherapy-benefits-foster-excitement-in-bladdercancer-despite-low-response-rates [Accessed 21 Apr. 2018].