Genomics could cut costs in the future

On 6 February,2024 | In Features

Dr Tim Woodman

While the field of genomics is already having a significant impact on oncology – and this is only set to increase – significant innovation will affect the treatment space over the next ten years.

Dr Tim Woodman, medical director of policy and cancer services at Bupa UK Insurance, reports in the first of a two-part analysis.

There are five key areas with the potential to have the most significant impact for us at Bupa and other healthcare providers.

In this feature, I’m going to explore the first three in more detail:

Liquid biopsies, including multi-cancer early detection tests;
Cell and gene therapies;
Cancer vaccines;
Digital oncology;
Artificial intelligence (AI) in cancer care.

Liquid biopsies, including cancer early detection tests

Liquid biopsies are increasingly being used in clinical practice. They are tests to diagnose or analyse tumours using fluid samples such as blood, saliva or urine rather than a solid piece of tissue.

They offer a personalised approach to cancer detection and treatment that is minimally invasive and could enhance patient outcomes and potentially reduce cancer care costs.

A subset of liquid biopsies are multicancer early detection (MCED) tests. They represent a significant potential shift in cancer care, enabling the simultaneous detection of numerous potential cancers.

This capability not only enhances early detection but also revolutionises our approach to comprehensive cancer screening.

Liquid biopsies can test for a single type of cancer or a MCED test can check for many different types of cancer in a single test.

They also have the potential to play a role in the triage of cancer patients, where those who require urgent care are prioritised.

Early assessments

While it is challenging to refer patients with non-specific symptoms of cancer for further testing, an affordable liquid biopsy triage – ideally able to detect multiple cancers – could be used with these patients to allow for rapid early assessments and investigations.

Although liquid biopsies may increase the number of patients who have abnormalities referred for further investigation, this may also contribute to increased efficiency, reducing time to diagnosis and potentially the costs associated with some late-stage therapies.

Benefits of liquid biopsies are:

Offering advantages in real-time monitoring, understanding treatment response and tailoring personalised treatment plans so that ineffective therapies can be avoided.

Potential ability to identify other biomarkers such as ribonucleic acid (RNA), proteins, tumour cells and extracellular vesicles.

Being less invasive for patients than traditional tissue biopsies.

A depth of insight through minimal residual disease (MRD) detection currently unseen within standard clinical practice and long before relapse can be picked up via traditional methods, such as imaging.

It may increase the understanding of tumour presence and changes over time, potentially offering a more sensitive and specific approach to cancer treatment.

The current drawbacks of liquid biopsies include:

The risks of false-positive results in MCED tests, indicating that someone has cancer when they do not, and tests may not always accurately distinguish between benign conditions and early-stage cancer. The likelihood of a false-positive result is greatest in those who are at the lowest risk of cancer.

False-negative results may occur, providing patients with a false sense of security and potentially delaying necessary treatment.

Discovering cancer-related information through screening tests can lead to emotional and psychological distress for patients and their families. So there will be a need to establish well-defined onward care pathways for them.

Even if the MCED test correctly detects the cancer, it may not provide precise information about the location, the extent and aggressiveness of the disease; therefore, further investigation, such as imaging studies may be necessary.

They could ultimately increase diagnostic procedures, rather than minimise the number of steps in the pathway to diagnosis.

Further validation is needed to establish test accuracy, reliability and cost-effectiveness. However, in future, as liquid biopsies become more reliable and cost-effective, we may lean towards using MCED tests, particularly in cases where there are non-specific symptoms of cancer and there is no alternative screening programme.

Currently, there are eight commercially available MCED tests, and at least another 20 in development.

At Bupa UK Insurance, we are partnering with Signatera to offer our customers tests for breast, colorectal and prostate cancer, and with Informed Genomics to give customers access to the Galeas bladder cancer test.

This urine test will help reduce the need for unnecessary cystoscopies in diagnosing bladder cancer. And The Cromwell Hospital in London is offering the TruCheck Intelli MCED test as part of a controlled pathway overseen by multidisciplinary teams.

First-line tool

As the technology develops and is validated, MCED tests will likely be used as a first-line tool for the early detection of cancer in tailored populations, followed by other testing, if needed – for example, to confirm the exact location of a tumour. This may improve patient outcomes and could decrease costs in future.

The use of liquid biopsies for monitoring cancer recurrence is likely to be adopted at scale earlier than its use in diagnosis.

Clinical trials are currently looking into liquid biopsies to monitor lung, breast and oesophageal cancer. It is anticipated they may be available by 2026.

They will also be a valuable tool to monitor treatment response, potentially replacing traditional blood tests and expensive imaging procedures for certain types of cancer.

In combination with AI, liquid biopsies will allow the development of an individual imaging plan for each patient, enabling less exposure to radiation for those with minimal risk of recurrence, which will likely decrease diagnostic waiting lists.

Cell and gene therapies

Cell and gene (CG) therapies have the potential to provide lasting treatment.

They can be tailored to the patient’s needs, paving the way for a more precise approach that can lead to better outcomes. These therapies could reverse or stop the progression of cancer and may significantly improve quality of life for patients.

Cell therapies involve the use of cells to treat or prevent disease by various methods, such as CAR-T therapy, stem cell therapy and tissue engineering.

While some cell therapies aim to replace or repair damaged cells with healthy ones to restore normal functioning, some such as CAR-T therapy enhance the patient’s own T-cells by genetically modifying them to target and attack specific tumour cells.

Gene therapies use genetic material such as DNA to treat a disease by permanently altering the gene known to cause the disease.

This is done by adding or modifying genes to correct genetic defects or providing cells with the ability to produce therapeutic proteins.

Gene therapies can be broadly divided into somatic gene therapy and germline gene therapy. Somatic gene therapy affects only the patient being treated, whereas germline gene therapy doesn’t only affect the person but also their descendants.

Clinical trials

Currently there are more than 500 ongoing clinical trials for CG therapies for cancer registered with ClinicalTrials.gov.

Although the majority are in early phases, advanced programmes have been put in place by regulators such as the United States Food and Drug Administration (FDA), European Medicines Agency (EMA) and Medicines and Healthcare products Regulatory Agency (MHRA) to accelerate the development of these therapies.

While the initial cost of these therapies continues to be high, the potential benefits include reduced treatment frequency and the need for prolonged hospital stays.

With uptake is rapidly growing, many challenges remain to effective implementation and patient access for CG therapies. These include:

The high cost of CG therapies. CAR-T therapy for cancer currently costs around £370,000 for a single patient. Expanding their use to earlier lines of treatment may expand the number of people receiving them, increasing overall costs.

Introducing more of these therapies into the market would also put pressure on healthcare systems, particularly if they are not curative and a second CAR-T therapy is needed.

Ongoing trials exploring cost-effective approaches are expected to complete in the next year.

Ethical concerns around the accessibility and equitable distribution of CG therapies have been raised. Their high cost and limited geographic availability have the potential to exacerbate health disparities.

Regulatory approval of CAR-T therapies often stems from early access programmes which rely on lower level of evidence from earlier-phase clinical trials. This introduces uncertainty about the safety and efficacy of both current and new CAR-T therapies.

Ongoing confirmatory trials, required by their early approval, may reduce this uncertainty in the coming years. The quality of life after CAR-T treatment is still poorly investigated.

Regulation for CG therapies is complex and continues to evolve across different regions, despite manufacturers and providers requesting consistency across regulatory pathways.

Much has been written about the distinctive characteristics of CG therapies and the need for new health technology assessment (HTA) methods.

It is expected that more CG therapies will be approved and used in an increasing number of cancers.

Cancer vaccines

There has been a growing interest in cancer vaccines due to recent advances in vaccine technology and the lessons learned from mRNA-based Covid-19 vaccines.

The large-scale production and distribution of RNA-based Covid-19 vaccines provided valuable
lessons in manufacturing, distribution and logistics, which can be applied to cancer vaccines. Other vaccine delivery methods rather than RNA – such as DNA and peptides – are also being studied and may be promising.

Cancer vaccines can be designed for both prevention and treatment of cancer.

Preventative cancer vaccines can significantly reduce the incidence of certain types of cancers, supporting a preventative care approach and helping healthcare organisations reduce the number of people becoming unwell.

These vaccines are designed to prevent the development of cancer by targeting a specific virus or other risk factors that can lead to the development of cancer. They can be used to prevent cancer from occurring in high-risk individuals or populations.

Two types of preventative cancer vaccines have been approved for many years:

The HPV vaccine protects against the human papillomavirus (HPV) which can cause some types of cancer, such as cervical cancer;
The hepatitis B vaccine protects against the hepatitis B virus (HBV), which can cause liver cancer.

There is a drive to boost uptake of existing preventive cancer vaccines. The NHS aims to eliminate cervical cancer in England by 2040 by increasing uptake of both cervical screening and the HPV vaccine. This will include offering the HPV vaccine in libraries and sports centres as part of a catch-up programme.

Preventive cancer vaccines for breast, colorectal and lung cancer are in early clinical trials that are expected to be completed between now and 2029.

If more preventive cancer vaccines become widely available, it is expected there will be a significant reduction in the incidence of certain types of cancer.

Therapeutic vaccines

Therapeutic cancer vaccines can be customised to target a patient’s specific cancer, allowing for more personalised and effective treatment approaches.

They may have fewer side-effects compared to traditional treatments and potentially reduce the need for more aggressive treatments, leading to improved outcomes and quality of life.

Therapeutic cancer vaccines are designed to train the immune system to attack cancer cells within the body.

Some have already been approved by regulatory bodies for use in certain types of cancer, such as prostate cancer (FDA), bladder cancer (FDA and Therapeutic Goods Administration) and advanced melanoma (FDA breakthrough designation, EMA priority medicine designation).

Cancer vaccines are being used in combination with other treatments, such as chemotherapy, radiotherapy and immunotherapy, to improve efficacy and reduce toxicity. Combination approaches may be particularly useful in treating metastatic disease.

In February 2023, the FDA awarded breakthrough designation to the combination of a personalised cancer vaccine and a monoclonal antibody (immunotherapy) for the treatment of patients with advanced melanoma following surgery who are at a high-risk of relapsing.

Vaccines in trials

There are over 300 therapeutic cancer vaccines in clinical trials. Early-phase studies are demonstrating promising efficacy of vaccines for colorectal, lung, gastric and pancreatic tumours. Researchers believe these vaccines will become widely available by 2030, but some believe that may happen earlier.

Future personalisation of cancer vaccines could allow them to be tailored to each individual’s specific cancer, allowing for more targeted treatment without affecting healthy cells. This theoretically will reduce side-effects and the need for longer periods of treatment, which can often be unpleasant.

Cancer vaccines will increasingly be combined with other therapies to enhance treatment success. Early-stage clinical trials are looking into using a cancer vaccine with CAR-T and other types of immunotherapy.

The UK government and BioNTech recently signed a partnership aimed at providing personalised cancer vaccines to up to 10,000 patients by 2030.

BioNTech clinical trials are targeting a variety of cancers, including melanoma, lung, prostate, and head and neck cancer.

Conclusion

These new technologies offer a more personalised approach to cancer prevention, minimally invasive diagnosis and more targeted treatment.

They have the potential to reverse or stop the progression of cancer significantly improving quality of life for patients and greater treatment precision will potentially reduce debilitating side-effects and cancer care costs.

See ‘A magic bullet for everyone?’