Innovation through immunotherapy10/08/17Health
PEN explores the innovation within oncology delivered through immunotherapeutic approaches, its potential and its complications
A new form of medicine which boosts the human immune system to fight tumours – immunotherapy – has been recommended for use. Studies have shown that it reduced the risk of disease progressions, or death, by 50% in comparison to chemotherapy. Immunotherapeutic approaches have been proven in clinical trials to effectively treat patients with bladder, head and neck, kidney, and lung cancers, as well as leukaemia, lymphoma and melanoma. Clinical trials are ongoing for more than 25 other types of cancer.
Immunotherapy can function in a variety of ways, including: stopping, or slowing, the growth of cancer cells; stopping the spread of cancer; and helping the immune system to work better at destroying cancerous cells. There are also several types of immunotherapy treatment: monoclonal antibodies; non-specific immunotherapies; oncolytic virus therapy; t-cell therapy; and cancer vaccines.
Advances in treatment
Pembrolizumab – previously accessible as a first-line lung cancer treatment under the Early Access to Medicines Scheme – can now be prescribed to patients with a particular type of advanced lung cancer who have already undergone chemotherapy. The drug is also used to treat skin cancer which has spread or can’t be removed with surgery. The National Institute for Health and Care Excellence (NICE) made its decision to recommend the drug after studies carried out by the manufacturer MSD showed it to reduce the overall risk of death in certain patients by 40% compared to chemotherapy. The treatment will be delivered to patients into the vein as either a drip or a long plastic tube into the chest.
The treatment will be available through the Cancer Drugs Fund, which was established to allow patients faster access to innovative cancer drugs. Professor of immunotherapy at the Institute of Cancer Research, Alan Melcher, told The Independent: “We still need to do lots of work to optimise how this treatment is used, and there’s an awful lot we don’t understand about which people will respond best. This supports the tantalising prospect of long-term control of solid advanced tumours using immunotherapy.”
Pembrolizumab costs over £1,000 (~€1,110) per 50 mg with the recommended treatment being 200mg by intravenous infusion every three weeks. Further survival data from the ongoing clinical trial by Public Health England is anticipated to determine whether the treatment is cost-effective for NHS implementation.
On 2 August, the Cancer Research Institute (CRI) – North America’s largest non-profit organisation and leading international funder of immunotherapy research – and Israel Cancer Research Fund (ICRF) announced the establishment of The Immunotherapy Promise™ fund. The collaborative campaign will dedicate support to Israeli cancer research.
The Immunotherapy Promise is an initiative dedicated to identifying and funding the most promising cancer immunotherapy research conducted in Israel. Private sector support for cancer research in Israel is not commensurate with the quality of Israeli science, and each year many promising research proposals are left unfunded. A joint review panel consisting of CRI’s Scientific Advisory Council and ICRF’s blue ribbon scientific review panel will meet annually to vet and recommend funding for the most deserving immunotherapy investigations across Israel.
Jill O’Donnell-Tormey PhD, CEO and director of scientific affairs at CRI, said: “We hope our collaboration will attract the best scientific minds in Israel to focus on immunotherapy research, while also offering Israeli researchers unique opportunities for sharing knowledge, exchanging ideas, and fostering new collaborations worldwide.”
ICRF president, Rob Densen, added: “We believe we are in the midst of a watershed era for immunotherapy and that this ground-breaking partnership has the potential to yield breakthrough research while building long-overdue appreciation and recognition for Israeli cancer research.”
Initially, The Immunotherapy Promise will fund four two-year immunotherapy projects in Israel, whilst additional grants are anticipated to be made as funds are secured. CRI and ICRF are opening a call for applications and expect the first grants to be awarded in the first quarter of 2018.
Mitigating economic risk
A trial to study whether a pair of immunotherapy medicines – Imfinzi, and experimental drug tremelimumab – would treat a form of lung cancer was initiated by British-based pharmaceutical manufacturer AstraZeneca, wherein combination treatments are anticipated to offer a therapeutic benefit to patients. In interim findings, it was reported that the manufacturer’s combination did not offer improvement on those therapies which already exist on the market. AstraZeneca shed 15% of its market value in a single day as an estimated £10bn (~€11.1bn) was lost on the results of the trial.
The industry believes that collaboration is needed in immuno-oncology as the market becomes saturated with developing therapies. Merck have purchased half the rights to AstraZeneca’s Lynparaza, in a deal worth $8.5bn (~€7.2bn). Resultantly, the pharma firms will co-develop and sell a drug known as a PARP inhibitor.
Cancer cells develop resistance by downregulating the features which immune cells use to detect cancer cells, including tumour antigen presentation through MHC class I molecules. Molecules present tumour-specific peptides on the surface of cancer cells so that they become visible to the immune cells, and specifically T-cells. Cancer cells produce specific immune molecules whilst triggering immunosuppressive processes. The interaction of these changes makes cancer cells virtually invisible to immune cells, whereby immunotherapy treatment is rendered ineffective.
A team led by Onur Boyman, director of the Department of Immunology, University Hospital Zurich, Switzerland, has discovered that the epigenetic control protein – Ezh2 – plays a central role in how cancer cells develop resistance. Researchers demonstrated that the tumour mass shrinks during treatment of malignant skin cutaneous melanoma with checkpoint inhibitors, or immunostimulating interleukin-2 therapy.
Over an extended period of time, skin cancer cells produced more Ezh2. As a result, antigen-presenting MHC class I molecules and the antigens specific to skin cutaneous melanoma were suppressed whilst activity of immunosuppressive modules which curb immune cells simultaneously increased. Consequently, the cancer cells were nearly invisible to the immune system and resumed reproducing in an uncontrolled manner. As reported in European Pharmaceutical Review, Boyman said: “As soon as we blocked the activity of the epigenetic regulator Ezh2 with a pharmacological inhibitor, the efficacy of the immunotherapies improved. The tumour masses shrank more significantly and the tumour-free survival was extended.”
Published in the Journal of Clinical Oncology, a trial on 100 kidney cancer patients analysed the response to a combination treatment of two immunotherapy drugs. Researchers found that the addition of ipilimumab, to the FDA-approved nivolumab, resulted in responses that can last beyond two years. Prior to the trial, half of the participants had metastasis which grew whilst undergoing previous therapies, however, when using the combination treatment, response rates increased from 20% to 40%.
In Specialty Pharmacy Times, Dr Hans Hammer, a Medical oncologist focusing on kidney cancer from UT Southwestern Medical Centre, US, said: “Durable responses lasting many years can be achieved with immunotherapy; while the side effects of immunotherapy can be significant, they are typically reversible and, unlike current therapies, don’t significantly dampen patients’ daily quality of life.”
Kidney cancer is the sixth most common type of cancer, affecting both men and women. It can be difficult to treat as standard chemotherapy produces minimal results and targeted therapies – which offer prolonged life expectancy – are associated with daily adverse effects. Single-agent immunotherapy treatments improving survival, however, are only beneficial to a subset of patients.
Currently, the combination immunotherapy treatment using nivolumab and ipilimumab is FDA-approved to treat melanoma, whilst it is undergoing testing for use on other types of cancer.
|Partnerships for progression
The Toronto Recombinant Antibody Centre (TRAC) from the University of Toronto, Canada, has agreed to licence Indian-based MedGenome’s patented cancer immunotherapy solution, OncoPept, to develop biomarkers for drug candidates against immune modulators to treat cancer. The licensing will form the foundation of a larger-scale partnership between the two organisations which can be used to provide antibody drugs to Indian markets.
Founder of MedGenome, Sam Santhosh, said: “TRAC has the best platform in the world for producing novel biologics. We are proud to partner with them by providing our OncoPept solution which can also help pharmaceutical companies select the right patients for their clinical trials.”
MedGenome is a leader in genomics research and diagnostics, capturing over 80% of NGS-based diagnostics in the Indian markets. Moreover, it has developed patented algorithms and pipelines to identify cancer vaccines to select tumours that will respond to cancer immunotherapy drugs, for example, checkpoint inhibitors.
Dr Sachdev Sidhu, professor at the University of Toronto, said: “MedGenome’s pipeline to dissect the tumour micro-environment at a molecular level will help in identifying new targets for which novel antibodies can be made”.
The partnership will strengthen TRAC’s drug discovery and development pipeline through incorporating genomics data to advance understanding of diseases at a molecular level, subsequently creating better medication and biomarkers for personalised therapies.
This article will appear in issue two of Pan European Networks: Health, which will be published at the end of August.