Written evidence submitted by Novartis UK (FCR0062)

About Novartis

Novartis is a leading global medicines company, which uses innovative science to create transformative treatments in areas of great medical need, with a long heritage in oncology innovation. In the UK, we employ approximately 1,300 people, and we are a leading sponsor of clinical trials. From research to delivery, we are a valued partner in the healthcare ecosystem, helping to build solutions that provide better care and access opportunities for patients in the UK.

Q1: What are the innovations with the greatest potential to transform cancer diagnosis and treatment in the short, medium and long term?

Although significant advances have been made in our understanding of cancer and its treatment, cancer remains the leading cause of death in the UK, with expected cases to grow by over 30% between now and 2040.[1]  Novartis believes that the greatest innovations will be seen in precision medicines and new treatment approaches such as radioligand therapy, cell and gene therapies, and immuno-oncology. 

Targeted therapies and precision medicine:

The advancing understanding of the biology of cancer has helped to tailor treatments to specifically target the tumour.  Targeted therapies treat cancer by blocking the pathways or mutations that drive tumour growth.  Precision medicine for oncology focuses on matching the most accurate and effective treatment to each individual cancer patient based on the genetic profile of the cancer and the individual, utilising companion diagnostics. 

Precision medicine is still in its infancy with many advances to come and with potential to demonstrate the impact of targeted therapies across the cancer pathway and across cancer types. For example, new approaches to adjuvant therapy will enable clinicians to use targeted therapies originally developed to treat metastatic cancer earlier in the pathway to prevent cancer from recurring.

To realise the potential of these innovations, all health system partners need to work together to ensure adequate testing capacity and rapid turn-around of and equitable access to molecular diagnostics; effective bioinformatics to support the management, processing and analysis of data; and improved medicines access policies, particularly flexible pricing for medicines with multiple indications.

Radioligand therapy

Nuclear medicine, using targeted radiopharmaceuticals to image and treat diseases, is an evolving speciality of medicine that is leading to both earlier diagnoses and more effective treatment options for patients with cancer.[2]  Radioligand therapy (RLT) is a type of nuclear medicine that works by delivering targeted doses of radiation to cancer cells.[3] This minimises damage to normal cells - unlike more traditional cancer treatments like chemotherapy.[4]  Whilst RLT is currently licenced for use in a small patient population in the UK,[5] the treatment has the potential to be applied to multiple cancers with much larger patient populations, with over 30 RLTs in Phase II/III trials across multiple companies.[6] RLT therefore represents a new modality for oncology treatment for which the NHS will need to prepare.

As highlighted by the Intercollegiate Review of Molecular Radiotherapy, there is currently regional variation in access to RLT services, as with some patients forced to travel nearly 200 miles for treatment.[7]   Expansion of RLT services, like other molecular radiotherapy services, will require purpose-built, shielded rooms. In terms of workforce, highly trained nuclear medicine specialists, clinical/medical oncologists, nurses and physicists working within an MDT are also required to deliver RLT.[8] An estimated 35 centres will need to be set up by the end of 2023 in order for all eligible patients to receive treatment.[9] This additional infrastructure and capacity would also support the delivery of molecular radiotherapies beyond RLT.

April 2023

Cell & Gene Therapies

Cell therapy and gene therapy are overlapping fields of biomedical research and treatment. With cell therapy, cells are cultivated or modified outside the body before being injected or infused into the patient, where they become a “living drug.” With gene therapy, genes are replaced, inactivated or introduced into cells—either outside or inside the body—to treat a disease. Both therapies aim to treat, prevent, or potentially cure diseases, and both approaches have the potential to alleviate the underlying cause of genetic diseases and acquired diseases.

Cell and gene therapies have demonstrated their potential in rare diseases with well-defined genomic targets, high unmet need, and small numbers of patients; nonetheless, there is great potential for the expanded application of these treatments in larger indications.[10] For example, with CAR-T cell therapies, patients’ own immune cells, T-cells, are re-programmed to make them better at detecting and killing cancerous cells. Current CAR-T research focuses on improving efficacy and safety, as well as exploring new targets to bring this potentially curative treatment to more patients.

Immuno-Oncology

Immuno-oncology could help provide a solution to cancers that don’t respond to traditional therapies or to cancer that recurs by harnessing the immune system’s ability to recognise, target and eliminate cancer cells. Through combination therapy and addressing the barriers to its use, immuno-oncology treatments could help tackle the rising number of worldwide cancer cases. Because they harness the body’s immune system, immunotherapies offer the potential for long-term, quality survival in a wide array of cancers.

Researchers recognise that the tumour microenvironment, may be as important to consider as the cancer cells themselves.  Tumours are masters of defence and deception, evading the immune systems with many molecular signals which can alter immune behaviour in multiple ways. Researchers are exploring mechanisms to strip away these signals and activate immune cells in the tumourin order to increase the immune response to cancer.   

Immuno-oncology therapies could become a cornerstone of cancer treatment in the future, and health systems should ensure that clinical pathways are rapidly developed and challenges for access, addressed.

Combination Therapies in Oncology

Combination of targeted therapies in cancer have become increasingly common, and the trend is expected to continue, with 150+ ongoing trials studying checkpoint inhibitor combinations in 2021.[11]  Adding new therapies (add-on therapy) to product(s) already on the market (backbone therapies) can deliver superior clinical outcomes by manipulating different mechanisms of action or multiple pathways across the tumour response cycle in numerous cancers. 

The growing importance of on-patent combinations poses unique challenges to existing value, pricing and reimbursement frameworks, which have traditionally been geared up to deal with medicines used as single therapies. Current systems still rely on assessing combinations as single technologies, which means combination therapies often struggle to demonstrate value, despite their potential to improve patient outcomes. 

Work is needed, involving all relevant stakeholders such as HTA bodies, industry and wider policy-makers, to address various challenges including value apportionment, indication level pricing and competition law constraints, and carve out a pathway for better access to combination therapies.

Q2: How best can innovations in diagnosing and treating cancer be transitioned into frontline clinical settings?

Capacity

With growing demand for cancer treatments, increasing specialisation and complexity of cancer care, and existing backlogs in oncology services, addressing capacity challenges is fundamental to ensuring that innovations can be transitioned to frontline services.  See Q4 for additional comments. 

Clinical research

A key pillar in the development of transformational treatments are clinical trials, particularly vital for those cancer patients with limited therapy options in routine care.  However, it has become increasingly difficult to conduct clinical trials in the UK: the number of industry-led cancer clinical trials initiated in the UK has sharply declined in recent years, falling by 41% between 2017 to 2021.[12] In the context of growing global competition to attract commercial studies, the UK needs to ensure industry can set up trials quickly and efficiently and recruit more patients into studies. Simplified access to comprehensive datasets and patient records could enable remote monitoring, accelerate set up and improve recruitment.[13]  Novartis welcomes the Independent Review into UK Clinical Trials and looks forward to reviewing its recommendations.

Diagnosis & Testing:

Molecular profiling technologies, such as genomic testing, are revolutionising cancer diagnostics and treatment.  However, challenges remain with regards to equity of access to genomic testing and uptake of new tests in the NHS, limiting patient early access to innovative medicines. The NHS Genomic Medicine Service (GMS) is designed to provide consistent and equitable access to genomic testing for NHS patients across England, however, lack of knowledge on the referral pathway and requirements can impact the length of time taken to receive test results, ultimately impacting patient outcomes. Appropriate training and education are critically needed to support of implementation of the GMS.  There is also a growing gap between England and the devolved nations in access to such testing; strategic investment is required across the whole of the UK.                                                 

Access to Medicines

Currently, only 54% of European Medicines Agency approved products available in England can be accessed by all cancer patients. The rest are either unavailable or have ‘limited availability’, restricting access for some patients. In contrast Germany (100%), Italy (90%) and France (80%) all rank far above the UK with more cancer patients having improved treatment options available to them. Patients in the UK are missing out on accessing the latest treatment innovations.[14]

Innovation in cancer needs to be matched with evolved approaches to considering value and pricing of medicines.  The Life Sciences Vision committed to a highly ambitious NICE Methods and Processes Review; however, the final publication of the updated programme manual did not adequately enable critical changes needed to fulfil the vision. 

A variety of key challenges remain which hinder wider access to new cancer medicines, and more changes are needed to the way that NICE and NHS England appraise and commission cancer medicines so that NHS patients can get access to the latest cancer innovations.

• CDF: The Cancer Drugs Fund is a ‘managed access’ fund for new cancer medicines, providing early access to those medicines that appear promising but have only limited evidence available at the time of their evaluation.  While the CDF exists to deal with some of access challenges, it does not address longer-term uncertainty or affordability. Furthermore, rare cancer treatments are unlikely to be eligible for CDF funding due to small patient numbers which can limit the ability to meet data collection requirements in the CDF.  Therefore, we must enable more flexibility in the pricing of medicines to ensure that England can keep pace with comparative countries internationally and also trial new innovative payment models. 

• NICE Methodology
• Uncertainty: Some innovative medicines struggle to be approved when assessed by NICE because of their limited evidence base. This issue can often be amplified for highly innovative medicines and those treating smaller patient populations, such as rare cancer medicines.
• ICER Threshold: The cost-effectiveness threshold used in technology appraisals remains unchanged since the establishment of NICE which means that the NICE threshold has declined in real terms by 37% since 1999.  The case for increasing the threshold should be considered to enhance wider access to more technologies. 
• Severity Modifier: The recent introduction of the severity modifier to replace the end-of-life modifier was meant to expand consideration of higher thresholds across a wider array of medicines based on disease severity; however, it has been implemented in a restrictive and cost-neutral way, meaning its impact will be limited, and medicines treating patients at the end of their lives (such as some cancer patients) are no longer valued to the same degree.  Further work is needed to ensure the new modifier can better support access to medicines.
• HST Criteria: Rare cancer medicines may not be eligible for Highly Specialised Technology (HST) evaluation because of the narrow entry criteria required.  There is a significant gap between the thresholds used in HST vs standard appraisal, and more flexible criteria are required to ensure that medicines for rare cancers have better chances for achieving positive NICE recommendations.
• Discount rate: Despite NICE endorsement and supportive Treasury Guidance, a modified discount rate for use in economic modelling for innovative medicines has still not been adopted.  Solutions to resolve this anomaly must be found, so that medicines which bring value over the longer term can be appropriately valued.

• Indication based pricing: An increasing number of new medicines are effective at treating multiple medical conditions or indications. In many instances, multiple price points may be needed for different indications to reflect the different value to patients and payers that each indication offers. The current criteria within the NHS Commercial Framework are designed to only allow IBP flexibility by exception can restrict access to indication-based pricing for some new indications.  Furthermore, the requirement set out in the NHSE Commercial Framework that innovators must offer additional value (ie, lower-than-standard ICER) makes accessing indication-based pricing more challenging, particularly for rarer cancer indications where paucity of data is already leading to high levels of uncertainty and thus, lower prices.

• Combination pricing: As noted above, the growing importance of on-patent combinations poses unique challenges to existing value, pricing, and reimbursement frameworks.  Work is needed, involving all relevant stakeholders such as HTA bodies, industry and wider policymakers, to address various challenges including value apportionment, indication level pricing and competition law constraints, and carve out a pathway for better patient access to combination therapies.

• VPAS: The Voluntary Scheme for Branded Medicines Pricing Access (VPAS) has led to rapidly escalating, unsustainable payment rates and is contributing to a highly challenging commercial environment for launching new cancer medicines. Agreeing a new Scheme that supports patient access to innovation is critical to transform the UK into a science superpower and improve outcomes for NHS patients across the whole country.

Uptake of Medicines:  Uptake of new medicines in the UK tends to be lower in the first five years after the launch of a new medicine, than in other countries.[15] On average, for every 100 patients in comparable countries who get access to a new medicine in its first year of launch, just 58 patients in the UK receive the same; this rises to 81 patients by year 5.[16]  Systems need to be in place to drive uptake following positive HTA guidance. This should include early health system engagement in regular horizon scanning and potential collaboration with industry partners via joint working projects which enable New Medicines Services to support adoption of innovation, increase uptake and adherence to new treatments.

Q3. What can be learnt about innovative cancer diagnosis and treatment from international examples of best practice?

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Q4. To what extent is workforce planning keeping up with innovations in the diagnosis and treatment of cancer?

It will be challenging for the aforementioned innovations to be delivered to patients without adequate workforce planning. The COVID-19 pandemic exacerbated existing pressures on the NHS workforce which was suffering from record workforce shortages pre-pandemic.[17] While increasing the flow of new trainees will be needed in the medium to long term, innovations in workforce models should be explored in the short term.

In a 2019 report on workforce from the British Society of Haematology, they noted that increasing incidence of haematological conditions combined with the complexity of new treatments requires an urgent review of workforce, particularly in light of expected levels of retirement and reduced trainees for consultant posts, with potential sever consequences of inadequate staffing levels.[18] 

The increasing specialisation and complexity of cancer care is necessitating greater sub-specialisation of health care professionals in order to deliver high quality diagnostics and care.  Workforce implications must be carefully considered and plans urgently developed to address recruitment, training, skill-mix as well as infrastructure. 

Q5. Is the impact of innovations in cancer diagnosis and treatment on health inequalities being sufficiently taken into account?

The disparities between areas with the highest and lowest cancer mortality are stark. Areas with higher deprivation also have higher mortality rates. Between 2017 and 2019, Manchester had 182 cancer deaths per 100,000 people compared to just 87 in Westminster.[19] A report by Cancer Research UK in 2020 also found that 30,000 cases of cancer per year are attributable to socioeconomic variations.[20]

As noted in NICE’s recent review of inequalities in breast cancer, “health inequalities exist between groups across different and often overlapping dimensions, including deprivation, geography, protected characteristics and inclusion health groups. These inequalities can be seen throughout the course of the condition, from health status and behavioural risk factors to the wider determinants of health and access to, experience of, and quality of care.”[21] These findings were corroborated by the APPG for Breast Cancer, which found high disparities in outcomes based on where people with breast cancer lived. It found that, based on where they live in England, a woman in the worst performing area may be more than twice as likely to die prematurely from breast cancer than a woman in the best performing area of the country.[22] This includes patients in areas with the worst outcomes being twice as likely to die from breast cancer than someone treated in another area. Geography also influenced a patient’s access to medicines and services to support related issues such as fertility, recovery and mental health.

Ensuring fast and fair access across the NHS to screening, diagnostics and treatment will ensure innovation is able to reduce inequalities, and this must be underpinned by high quality data, allowing clinicians better insight into patient pathways and helping to identify variations. The health system must work to improve the accessibility and integration of health data, and the Major Conditions Strategy should set targets to improve cancer datasets across the treatment and care pathway from clinical research to cancer outcomes.

We recognise that life sciences organisations have a key role to play in tackling health inequalities together with policymakers, healthcare systems and local communities. As an important contributor and partner to the NHS and wider UK healthcare ecosystem, Novartis are committed to playing our part in tackling health inequalities through partnership working.