Therapeutic areas in focus
A targeted approach to developing targeted blood cancer therapies
Edmond Chan, Senior Director, Therapeutic Area Lead, Haemato-Oncology for Europe, Middle East & Africa (EMEA) at Janssen, explores how precision medicine and targeted solutions can be utilised in the fight against cancer
Over the last decade, it has become increasingly clear just how heterogenous cancer is. Different cancers – whether they be multiple myeloma, chronic lymphocytic leukaemia, or beyond – have different unmet medical and patient needs, not just from each other, but also within their cancer type.
This has reinforced the critical need for a tailored, targeted approach to treatment and management, which have the potential to deliver individualised approaches to care – or, in other words, to target the right patient with the right treatment at the right time. These therapies hold the potential to change the standard of care trajectory.
On the other hand, the targeted nature of these new therapies brings with it an increase in the possible avenues for research and development, as we explore the many different genetic factors that could influence treatment. In the last five to ten years, we have already witnessed a significant growth in cancer research, particularly in the field of haematology. Ultimately, though, every organisation working within our industry has limits to its time and resources. We cannot
simultaneously innovate in every treatment route for every cancer type.
There is, therefore, a need for us to take a focused approach to innovating in targeted treatments, directing our efforts to those areas where the challenges are and that we know best, to give us the greatest chance of success. By focusing on areas that harness our expertise and experience, we can deliver meaningful improvements to the lives of those living with cancer.
The power of precision medicine
Precision medicine has been one of the areas that is becoming more and more prominent in our work in haematology. By taking into consideration cytogenetics, disease type, health status, and disease characteristics, it equips clinicians with bespoke treatment options and combinations that are tailored to the individual, allowing for a highly targeted approach.
This is already beginning to deliver successful treatments for those living with blood cancers, but the power of precision medicine is by no means exhausted. There remains significant potential to push the boundaries of current innovation, and we are seeing exciting new technologies in the field emerge all the time.
Of course, by providing a more nuanced approach, precision medicine is accordingly more complex to develop and deliver compared with traditional approaches, as it can involve many stages and stakeholders. Despite this added complexity, my view is that the potential advantages of precision medicine are worth it – and that we can give ourselves the best chance of success by taking a precise focus on developing treatments in certain disease areas where we already possess years of experience, and then apply the learnings in other disease areas in the future.
So where is precision medicine making a meaningful impact for people living with cancer? Chimeric antigen receptor T (CAR-T) cell therapy is one example – a therapy option that holds significant potential for people living with multiple myeloma who have few available treatment options, and are often faced with poor outcomes.
Despite the advances that have been made in care, relapse is still considered inevitable for those diagnosed with multiple myeloma, and, almost 40% of patients do not reach five-year survival.
Working by harnessing the power of a person’s own immune system to target cancer cells expressing a specific antigen treatment, CAR T cell therapy is a novel and highly personalised treatment.
Unsurprisingly, it is a complex process, requiring close collaboration between stakeholders across the industry to deliver it in the most effective way possible. But the need to harness this kind of innovation is clear – so we must
keep advancing to provide patients with this additional treatment option, as well as other ‘off-the-shelf’ targeted therapy alternatives such as bispecifics.
Delivering targeted solutions for patients
We recognise the importance of giving patients an active role and voice in the research and development process, and precision medicine is no different.
Receiving a cancer diagnosis can be overwhelming and frightening, often leaving patients with limited time – time that is impacted by the physical and emotional burden of living with cancer. Moving away from a one-size-fits-all treatment model offers an opportunity to start to try and alleviate this burden.
As well as having the potential to deliver better outcomes for extending life, such targeted therapies may also give people living with cancer time to do the things they enjoy doing. For instance, providing treatments that can be administered more rapidly and increasing the availability of oral treatments or subcutaneous injections versus intravenous formulations, means more flexibility for patients, less time spent in the hospital, and more time to spend doing the things that matter to them.
Realising the potential of targeted therapies to transform quality of life requires putting the patient voice and experience at the heart of treatment development. This can be achieved by working closely with patient organisations at each stage of the clinical trials process, including patient perspectives in health technology assessment decision-making, or providing the forums for people living with cancer to discuss their experiences of the diseases and treatments more broadly.
Change through collaboration
As treatments become more targeted, and lead to a corresponding growth of options based on different mechanisms of action, therapeutic indications, and influencing factors, the amount of information being provided to clinicians grows ever larger as well. The knowledge and expertise required of them, and of researchers working in the field, can also become increasingly specialised. To maximise the benefit to patients of such a targeted approach, we must work in collaboration with these experts from across the world – working towards our common goal of having new, efficacious treatments for cancers with high unmet need.
In other words, precision medicine can only have the impact that we hope it can have if we’re collectively able to translate scientific discovery into clinical practice. Thankfully, we are already seeing examples of this. For instance, the machine learning ledger orchestration for drug discovery (MELLODDY) project brings together academic and industry partners, to collaborate on an machine learning tool that pools insights from data generated during drug discovery programmes across the world.
This is particularly important for rare diseases, where individual clinical trials have a fixed number of patients involved, and often limited access to a larger patient pool. Projects that use increasingly sophisticated technologies to collate data more broadly, allowing healthcare professionals and researchers to identify trends within a greater population size that can have a direct impact on day-to-day clinical practice, are therefore incredibly useful. Other similar examples of this are the Haematology Outcomes Network in Europe (HONEUR), which is a secure, collaborative platform allowing the combined analysis of datasets in haematological malignancies, and the European Health Data and Evidence Network (EHDEN), another data-sharing system powered by data from more than 100 million records.
Progress is already being made, but there is of course more we can do. Change can only come through collaboration and, with research and development only growing more ambitious and complex, working with the wider oncology and haematology community and utilising exciting new technologies, such as AI and ML, are critical for success.
Targeting better treatments for the future
Precision therapies have potential as a future mainstay of treatment for haematology. As we move away from a one-size-fits-all approach, there is such scope to continue improving cancer therapies – and it is only by taking a targeted approach to developing these therapies, and working with experts across the region, that we can give ourselves the best chance of success. As the pace of advancement in precision medicine continues to accelerate, we will continue in our focused approach, targeting the areas in haematology that we have strong heritage in, and facilitating partnerships with the scientific community and wider oncology industry. The European Haematology Association Congress in June will provide another milestone on this journey, and will also give us further insight into what precision medicine holds in the future.
The last ten years have seen us make incredible progress in understanding cancer heterogeneity. The next ten years offer an opportunity to turn this better understanding into better outcomes for patients – but only if we target this opportunity in the most effective way possible.
Teoh PJ, Chng WJ, CAR T-cell therapy in multiple myeloma: more room for improvement. Blood Cancer Journal 11, 2021
De Angelis R et al, Survival variations by country and age for lymphoid and myeloid malignancies in Europe 2000-2007: results of EUROCARE-5 population-based study. Eur J Cancer 51: pp2254-68, 2015
Zhou X et al, Bispecific antibodies: a new era of treatment for multiple myeloma. J Clin Med 9: pp2166, 2020
joined Janssen in 2012 and has led multiple different functions in the organisation, including R&D, local, regional and global Medical Affairs. He currently heads the EMEA Medical Affairs Haematology team, focusing on haematological cancers such as multiple myeloma and chronic lymphocytic leukaemia, and driving patientcentered solutions and treatment in areas of unmet medical need. He is an experienced, UKtrained pharmaceutical physician, specialising in renal medicine, and holds a doctorate in clinical research in solid organ transplantation.
Supporting the challenges of innovative systemic treatments
Dr Stuart Hill, Medical Director, Merck UK & Ireland, highlights how the benefits of immunotherapy can be maximised to meet the needs of each and ever y
In recent years, we have seen significant innovation in the way that we treat cancer, as newer treatments such as immunotherapies, including CAR-T therapy and targeted therapies, have all brought with them a new set of challenges. These range from equity of access (stemming from practical issues around resources in hospitals hindering treatment delivery), to how best to manage complex immunorelated side-effects, and to the ongoing issues around biomarker testing. Many cancers have recently had new systemic treatments approved for use by the MHRA and recommended by NICE on the NHS, and brought to light these challenges faced by clinicians across the treatment pathway and throughout the healthcare system.
Service design adaptation is needed
As a result of the increasing number of patients being initiated on immunotherapies, for example, there is an increasing impact on overall clinic capacity. There aren’t suddenly more chemotherapy chairs and spaces that can be used to support these new treatments. Service provision and capacity needs to be addressed to accommodate the growing patient numbers. As more cancers are being treated with immunotherapy options, the number of patients treated with them will continue to grow. There is significant variance across the country on how service design is set up to support the provision of newer therapies – with some regions/models of care faring better than others.
There are also many ways immunotherapies are used, for example, as a single agent or as part of a combination treatment. This can also create challenges with the service capacity and timing of treatment. Patient experience also needs to be considered in terms of distance travelled to receive treatment, as well as the overall amount of time that they receive treatment.
While this will not change overnight, these issues need to be addressed and reviewed to ensure the potential benefits of immunotherapies can be fully unlocked. Although the pharma industry can’t necessarily offer support to improve service design, we have collaboratively worked with clinicians to bring to light the key challenges
and needs, and will continue to do so. We’ve also raised awareness and understanding among key decision makers who can use the clinicians’ personal experiences to create solutions.
Biomarker testing is on the increase
In addition to service design and provision, we have seen an increased use of biomarker testing, which brings additional challenges across the UK in terms of speed of testing, lack of consistency in testing across the UK, and how testing is funded and positioned in the treatment
pathway. These factors can impact how patients get the right treatment at the right time for their type of cancer. These challenges are not unique to any one tumour type, but are consistent across the board for immunotherapies, as well as the newer targeted therapies. Pharma has an important role to play in fully understanding the significance of testing, and in educating clinicians to ensure the best clinical outcomes.
Learning from clinical experience
We now have 10 years of follow-up data from the melanoma trials where immunotherapy was first used, and there is a clear long-term benefit of these treatments, including an increase in overall survival. All the lessons that we have learnt can be directly transferable to Genitourinary (GU) cancers, such as how to manage the side-effects, and how to best manage the treatment pathway and decision-making by the multi-disciplinary team. Whilst we’ve got to wait and see the long-term outcomes in other cancers, we shouldn’t assume that because it’s happened in one cancer type that it’s going to happen elsewhere. However, the data as it stands does potentially indicate a similar trend. Whilst we wait for long-term data, pharma has an important role in collating real-world evidence to support the use of immunotherapies, and to continue to inform clinicians on the benefits of these treatments, along with how to interpret the data that is continuing to emerge.
Support required for all in managing side effects
Managing the side-effects of immunotherapy is one of the biggest clinical challenges. Successful management is critical to both patient outcomes and the patient experience. Managing side-effects appropriately can only be done if there is an understanding across the wider clinical team of who may encounter a patient during treatment, such as A&E and acute care. There are many healthcare professionals (HCPs) who need educating on understanding the toxicities associated with immunotherapies, and appreciating that they are very different from chemotherapy, where they may have more knowledge and experience. There is an opportunity for larger teaching hospitals who have more experience, to help support smaller regional/district hospitals in helping manage side-effects appropriately. This specialist knowledge is something that is only acquired through experience, and it’s important to recognise that with any newer therapy, education is key to ensuring the best patient care.
How pharma can help
At Merck, we are committed to providing good quality information for HCPs. With innovation comes some form of challenge, and there is a need to ensure that information is provided to ensure the best possible clinical and patient outcome.
It is our duty as an industry to help support and provide guidance to HCPs, who are part of a treatment pathway on how to manage care with these new systemic treatments, and how to best deal with the complex needs of patients.
There is a focus on sharing best practice to support some of the themes already mentioned around service design to deliver the best care to their patients. With there being such variance across the country in the way that things are done, anything that we as an industry can do to help bring equity of delivery in the care pathway is important. At Merck, we have several initiatives working closely with HCPs to capture key learnings and best practice. These are developed into resources and content that are shared across different audiences, to help drive discussion and address some of the areas where improvements to patient outcomes can be made.
With any new treatment innovation, pharma is instrumental in ensuring that the right studies and research are conducted that inform important clinical decisions – proving that outcomes will last in the real world, as we’ve seen in clinical studies. It’s also important that we set up trial designs that are innovative and forward-thinking – looking at how to best maximise the benefit of immunotherapy, using them as single and combination agents across different tumour types.
We must also ensure speed of access so that patients get the treatments as quickly as possible. We have a responsibility, to those patients who may potentially benefit to work closely with regulators and funding bodies, to minimise the time in those processes to speed up access.
NICE’s Innovative Licensing and Access Pathway process, launched last year, is a step in the right direction. The initiative allows companies to work with NICE and the MHRA much earlier in the development process, receiving advice and input on clinical trial design, to ensure optimal data generation for both regulatory approval and health technology appraisal. This process should lead to quicker market access for companies, and faster access to innovative medicines for patients.
With companies and key stakeholders in healthcare systems coming together to align quicker in decision-making and benefitrisk, clinical outcomes for patients should ultimately be improved.
Looking to the future
Given the body of evidence that is still emerging in long-term use of immunotherapies, closely evaluating the data to make sure we are personalising treatment, and understanding the drivers of treatment efficacy, is critical. Irrespective of what the systemic treatment is, the only way we are going to be able to do the best for patients in the future is by identifying the right oncogenic drivers that are causing the cancer to grow and develop, so that we can target the right intervention to stop it.
Dr Stuart Hill
is Medical Director, Merck UK & Ireland. In 2010, Stuart joined Merck and has worked for the last 10 years in the Oncology Business, which he has led as Business Unit Director for the last 3.5 years. The heavy focus on translating science into improved outcomes for patients has inspired Stuart to now take up the leadership of the Medical Affairs team for Merck’s UK & Ireland operation.
NHS waiting lists: the second healthcare crisis?
Roland Kreissig, Oncology General Manager at Novartis UK and Ireland, sits down with Pharmafile to discuss how COVID-19 affected patient access to cancer treatments, and how pharma can support the NHS to face this challenge
What challenges have the NHS faced in providing cancer treatments to patients over the last couple of years?
The last couple of years have provided endless challenges to patients and NHS staff – and we have all heard about increased waiting times and pressure across the healthcare system. As we learn to live with the realities of a post-COVID-19 world, we now face a second healthcare crisis, in which millions of people are waiting for NHS treatment. When thinking specifically about cancer care, every point along a patient’s journey through treatment has been affected by the pandemic – from delayed diagnoses, cancelled or postponed appointments, and concerns about coming into hospital for treatment, side effects, and follow-up. Cancer Research UK has been collecting data about what these delays really look like for patients, and they provide insight into the scale of the issue. They found that screening – crucial for early diagnoses in many cancers, like breast, bowel, and cervical – went down significantly in 2020/2021 when compared with 2018/2019, both in terms of those being invited, and those participating. In breast cancer, for example, the number of invitations was down 22%, and the number participating was down 33%, equivalent to almost 600,000 women. 1This same trend was seen in people waiting over six weeks for a diagnostic test, where in radiology the waiting in November 2021 was 16 times higher than pre-pandemic, with almost 200,000 patients waiting for their diagnostic test.
Even as we move back towards a ‘normal’ way of working, we all need to remember that the pressure on the NHS resulted in shifting and juggling priorities, with many patients waiting in the background for their turn. This backlog for appointments, tests, and procedures will continue to be felt across the country, with some estimating it could take until 2033 for the backlog to clear.
The NHS will need to manage this backlog, while also progressing and improving care for the future. From the perspective of a pharma company, there was also a need to adapt clinical trials so we could continue to develop treatments and go through approval processes, despite the massive changes in healthcare. This challenge will require bold solutions, close collaboration, and exciting innovation, to ensure cancer patients are receiving the care they need, when they need it.
At Novartis, we believe we are strongly positioned to help the NHS recover, during a time when collaboration is more important than ever. We have been working very closely with partners across the life sciences ecosystem to identify individual issues hindering the delivery of treatments, and to offer tangible solutions to address these to support patients and the NHS.
How can pharma companies support the NHS cancer backlog and improve patient access to cancer treatments as we continue to live with COVID-19?
The NHS has been leading the charge in the UK through the pandemic, dealing with unprecedented pressures, and looking to staff to fill many roles to keep clinics and services running. But if COVID-19 has taught us anything, it’s that if we are to bring about real change, we must collaborate like never before. Those in the private sector, including pharma companies, must provide the necessary tools and support to the NHS, giving frontline staff more resources to focus on their growing patient lists whilst also looking ahead to deliver for the patients of tomorrow.
These private-public collaborations are an opportunity for organisations with invaluable knowledge, technology, and resources to be used in collaboration with the NHS to support the backlog and help with innovation of care. At Novartis, our digital innovation lab, Novartis BIOME, identifies digital and data-led solutions to reimagine medicine for the better, and ensure no patient is left behind. For example, our newly-launched Evidence Lab has been set up through our Biome digital innovation programme to work within the health system and with health tech innovators, to test and validate digital health solutions, to see what the system would benefit from most, before investment in full-scale implementation.
What developments and innovations do you think will make the biggest difference to the NHS’ cancer care in the coming years?
The NHS has ambitious goals for providing improved care for patients, and as it is currently developing a 10-year plan for how it will tackle the biggest challenges in cancer care, we are pleased that Novartis has been able to actively participate in this process by providing our recommendations. It’s an opportunity for all players in the UK cancer space to reflect on our priorities for the future.
At Novartis, we plan to continue supporting the NHS by prioritising innovation across the patient pathway. As we move towards more personalised care, we see a real opportunity to radically reform cancer diagnosis. New diagnostics, innovative technologies, and genomics, can all support patients to reach a more accurate and faster diagnosis. This will in turn enable patients to access new treatment options, including personalised and targeted medicine.
Digital health solutions will become an important tool to not only speed up the diagnostics process, but also help track disease progression and symptom burden, empowering patients to be more engaged with their clinician and treatment decisions. For example, the myeloproliferative neoplasms (MPN) Tracker, introduced by Novartis, helps people living with MPNs to recognise symptoms, regularly track them, and start a conversation with their doctor. Additionally, by harnessing health data, we can ensure interventions can be both targeted and informed by behavioural insights, to ensure that they have the biggest impact on diagnosis. Moving forward, the health system must work to improve the accessibility and integration of health data across the treatment and care pathway, from clinical research, to cancer outcomes, and quality of life.
What lasting changes has COVID-19 had on the treatment of cancer?
With the rapid development of COVID-19 vaccines, we have seen the power of public/ private partnerships in addressing public health issues. We can now take the lessons learned through this process and apply them to improving care for cancer patients, to address the lasting changes of COVID-19.
For example, the long-term challenges in the treatment of cancer go beyond the immediate backlog of care that we are experiencing now. Not only do existing patients need to be treated, but there are new diagnoses and late presentations that need addressing simultaneously.
One way this is being addressed currently is through appointments being made digital, to provide easier and quicker access to HCPs. However, with more appointments moving online, how can we ensure communication remains at a high enough standard? This is an opportunity for private organisations to support the NHS with new and innovative solutions aimed at improving telehealth, so people have access to the same quality of care while speeding up the process.
is Oncology General Manager for Novartis UK and Ireland. He joined Novartis UK in January 2022, prior to which he held the position of Oncology General Manager for Central Europe.