Tuesday, 10 June 2014

ASCO 2014 - The emergence of non-specific immunotherapies for cancer

Several times now I have heard the phrase ‘we need a more holistic approach for treating cancer’ being used by specialist respondents during market research studies. These respondents often say that cancer requires a whole-body approach rather than the more targeted therapies available. Therefore, one of the key questions that researchers have been asking of late is: why does the immune system hold back against cancer cells? At ASCO last week, where our team went to present a workshop on brand immersion, it is clear that this holistic approach is starting to take the oncology field by storm.
Immune-therapy refers to a group of treatments called biologics. Biologics have two main modes of action: flagging and blocking. Antibodies that constitute immune therapy can work by flagging the hidden cancer cells to the immune system, for example Campath attaching to CD52 on T-cell leukaemia. Alternatively they can physically block a receptor, negating proliferation signals in cancer cells. For example, Herceptin binds Her2 receptor on mammary cancer cells and blocks epithelial growth factor (EGF) from activating a proliferation signal. These type of biologics have been designed to target specific molecules on cancer cells and this approach is now being replaced by more holistic approach which utilises the immune system.
Naturally, the immune system fights cancer. It is only when the immune system does not detect developing tumours that cancer prevails. For example, some of the side effects immune suppressants have are malignancies, or the incidence of non-Hodgkin’s lymphoma in (immunosuppressed) HIV patients. All of these indicate the role of the immune system in defending against cancers.
But the immune system has a complex status quo to keep. It has to attack pathogens, intrusions, and cancers, whilst at the same time avoid attacking the body.  To that end, the immune system has to train itself through life to give rise to immune cells that defend the body against pathogens and at the same time to rid itself of immune cells that may attack healthy organs (which is what happens in autoimmune diseases). The immune system has a complex mechanism with a lot of stops and guards to assure its efficient and safe operation. Some cancers evolve to find ways to utilise the stops and guards which provide immune tolerance to healthy tissues in order to evade detection.
Now Scientists in several pharmaceutical companies have chosen to try and kick start the immune system to fight cancer. Initial research even involved using a bacterial infection to activate an immune response that will kill the bacteria and then move on to the cancer.  In the last ASCO meeting a more clever way to ‘switch-on’ the immune system has taken over with several products in late development. All these new products target one or another of three molecules in the immune cycle pathway. PD-1 (Programme Death-1), PD-1L (Programme Death-1 Ligand) and (Cytotoxic T-lymphocyte associated protein 4 (CTLA-4). In this new approach, the treatments target the immune cells and their inhibitory markers, instead of attacking the tumour directly, once the immune system switches-on, it starts fighting the tumours. These revolutionary class of treatments could be used in various indications, because they are not cancer specific.

The main players in this field are BMS who have already launched Yervoy, an anti CTLA-4 antibody, and has an anti-PD-1 product in late stages (Nivolumab), which is currently being tested as a combination therapy with Yervoy in phase III trials. Additional competitors to enter the immune-cycle market are Merck (who received a breakthrough designation for their MK-3475), Teva/Curetech, GSK/Amplimmune and Roche who also received a breakthrough designation for their product.
The fact that so many companies chose to develop treatments to target the immune cycle indicate its importance, as this means that these treatments could be used to help in a wide variety of indications. It also means that late stage cancers that were previously untreatable because of a lack of specific therapies, can now be treated. Moreover, the healthy competition that is likely to arise through the introduction of several biologic treatments in this class, will certainly have an effect on price, market access, and the uptake of each product that will be licensed. We wait with baited breath for future developments.
But with the potential for broad indications, devising the right marketing strategy will become all the more vital to product success. 

We leave you with this question: How can these pharmaceutical companies create brand stories for their broadly licensed biologics that resonate with their key customers in each of the specific therapy areas?
In case you want to follow up
Merck’s MK-3475
Roche’s drug MPDL3280A
BMS’ Nivolumab and Ipilimumab (Yervoy)
GSK/Amplimmune’s Amp-224
Teva/Curetech’s CT-011
This article was written by Shai Senderovich, Research Executive at Branding Science

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