Curative cell and gene therapies and healthcare system disruption

In this article, experts from Charles River Associates discuss how the introduction of cell and gene therapies will impact upon various aspects of the healthcare system, from provision of care to delivery and supply, and pricing and market access.

3D rendering of embryonic stem cells in red and orange with purple nuclei - idea of curative cell therapies


Significant scientific advances have created a rich clinical research pipeline, with innovative and potentially curative cell and gene therapies already available (eg, Kymriah® for acute lymphoblastic leukaemia, Luxturna® for inherited retinal disease and Zolgensma® for spinal muscular atrophy). Over the next 10 years, more of these therapies are expected to enter the market for other disease areas and larger patient populations. Potentially curative cell and gene therapies represent a key shift in patient care and will have considerable impact across the patient journey, affecting the healthcare system as we know it and the key stakeholders involved. Their launch is also met with significant debate over the uncertainty of outcomes’ durability and safety over the longer term; and the impact of treatment prices on affordability as more treatments enter the market. We draw from the characteristics of treatments in the pipeline and discuss the implications these will have on elements of the healthcare system and stakeholders that are most likely to be disrupted. Specifically, we discuss the impact on provision of care, delivery and supply chain, pricing and market access and value demonstration — given the difficulty of proving a durable, curative effect.

To understand the extent of the disruption posed by anticipated curative cell and gene therapies, we assessed the current pipeline for curative treatments. Approximately 55 percent of trials for curative cell and gene therapies are in Phase II, hence, we would expect an increasing number of launches in the next approximately five to 10 years.1 Some of the disease areas with a significant number of assets in development include oncology, rare diseases, blood disorders, infectious diseases and cardiovascular diseases (CVDs); and launches into the more prevalent conditions, such as CVDs, would lead to a larger systemic impact on healthcare structures.

Implications of potentially curative cell and gene therapies for healthcare systems

The positive health and other indirect benefits from potentially curative cell and gene therapies will require significant changes to healthcare systems at a global level. Drawing from the implications in three distinct disease areas with significant expected launches — rare diseases, cardiovascular diseases and haemophilia—potentially curative cell and gene therapies affect the patient journey throughout the healthcare system.

Diagnosis: the need for earlier and targeted diagnosis

To realise the full benefits of curative treatments, patients need to be diagnosed early. This will require continuous support and broader access to newborn screening in disease areas with strong genetic links, such as beta thalassemia, and a more significant shift towards targeted genetic testing in diseases with later symptomatic onset, such as CVDs.

whole image filled with blue cells with orange nuclei - idea of cells for cell therapy

More than 80 percent of rare diseases have a monogenic cause and are biologically attractive targets for cell and gene therapies, as by re-coding the defective gene or altering gene expression they can be cured.2 With a potential beta thalassemia cure on the market, diagnosis through screening could offer the opportunity to identify and treat patients early so they could enjoy better health through their adulthood. This also may lead to significant cost offsets for care and increased productivity gains from patients’ economic and societal participation.

Alternatively, CVDs are heterogeneous and multifactorial, from demographic to lifestyle-based, with only a portion of CVDs having clear genetic factors.3 Diagnosis is often confirmed later in life and diagnostic medical testing is driven by lifestyle risk factors and personal or family medical history. Cell and gene therapies in development for CVDs rely on current diagnosis methods. Biomarkers are becoming increasingly important and there is potential for curative therapies paired with targeted testing to motivate earlier diagnoses and avoid later-stage healthcare costs.4,5

Contact with HCPs: need for expanded healthcare expertise

In the presence of curative therapies, the required level of healthcare expertise will change. Healthcare professionals (HCPs) involved in the current care process will either need retraining or moving to serving patient populations not targeted through cell and gene therapies. In addition, curative treatments often depend on complex processes of preparation and administration, requiring a new set of specialists to be trained.

there will be significant adjustments to current healthcare systems affecting diagnosis, treatment expertise and infrastructure…”

Looking at the current treatments for CVDs, these range from initial preventive treatment for those at high-risk of developing CVDs, to oral therapies prescribed in the General Practice (GP) setting (also referred to as ‘Family Practice’), to in-hospital procedures. As CVDs often eventually require long-term treatment through a mix of primary and secondary settings, the introduction of potentially curative cell and gene therapies could disrupt disease management and have implications for practitioners. In a world with CVD curative therapies available, GPs are less likely to treat/care for CVD patients who have early targeted genetic testing/diagnosis and specialists are likely to play a larger role in patient care. For example, standard treatment for coronary artery disease currently consists of generic oral products such as statins, which can be prescribed by the GP. However, a gene therapy in development for this disease, Generx® (currently in Phase III trials), requires administration through a balloon catheter by a specialist cardiologist.6 In addition, curative therapies could reduce the requirement for cardiologists to perform as many traditional CVD surgeries, if they are effective in stopping or reversing disease progression.

Building an appropriate hospital infrastructure and the role of cross-border care

The infrastructure required for the preparation, delivery and administration of curative treatments is highly specialised. This will likely lead to a clustering of care expertise and infrastructure needed for certified Centres of Excellence (CoEs) where care is delivered, with multidisciplinary teams providing integrated diagnosis, initial care and treatment maintenance services. It is also likely that these select centres may not be available in every country or region.

For rare diseases, treatment is largely provided at targeted CoEs that pool the necessary infrastructure and expertise. Although most rare diseases require life-long care, current standard of care treatments range from oral therapies to procedures and surgery. Potentially curative cell and gene therapies represent a complete shift in treatment, from chronic maintenance to a one-off or discrete course of treatment. In the example of beta thalassemia, emerging treatments would require extended stays in highly specialised facilities, which are scarce (eg, there is only one in Germany). Following the procedure, while patients will continue to be monitored by haematologists, cured patients would no longer need to visit clinics every two to four weeks for blood transfusions. This would represent a significant relief in burden and increase in quality of life for patients, plus reduce the specialist resources required for chronic treatment. Moreover, patient reliance on specialised treatment centres for chronic care would also decrease over time. Severe patients or those for whom the efficacy of curative treatments has waned likely would constitute most patients for these centres via on-demand factor replacement. This change in patients served would affect the market models, reimbursement opportunities and the portfolio of services that these chronic care specialist centres offer to patients.

Appropriate assessment of value and pricing and reimbursement

Given the long-term health and indirect benefits provided by curative treatments, health technology assessment (HTA) bodies and payers have already started to include the longer-term impact and broader benefits in their cost-effectiveness assessment modelling. They have started to explore more flexible approaches and thresholds to allow the value of curative therapies to be understood and tested over time. The degree of shift in methodology will vary by disease area and available treatment options.

Blue DNA strand inside a red and white capsule on a white background - idea of gene therapyFor rare disease treatments, a flexible approach encompassing special provisions or pathways is implemented in many countries to allow for a higher price and address limitations in evidence given the small patient populations. In more prevalent disease areas, with multiple treatment options and, in some cases, generic alternatives, HTA or other evaluating bodies will require a more significant shift in approach to allow for curative treatments’ benefits and costs to avoid suboptimal comparisons to existing therapies. For example, flexibility in comparator analysis will be required for CVDs, where standard-of-care is consistently oral treatments (eg, beta blockers, acetylcholinesterase inhibitors). Considering long-term cost offsets is also key. The need for ongoing surgeries and/or heart transplants, which particularly affects progressive diseases such as heart failure, could be replaced with curative medicines that could potentially reverse the progression, such as Revascor®, a cell therapy in Phase III for chronic heart failure.7,8 This may lead to indirect health benefits by reducing co-morbidities and increasing gains from productivity later in life.

Dealing with uncertainty and importance of data and registries

A key component that requires close consideration is how HTA bodies and payers deal with uncertain efficacy and safety data. Curative treatments have only recently launched and will require long-term studies, as well as monitoring and collection of real-world data (RWD) to demonstrate durability of effect and safety.

There is already a trend towards the development of RWD registries for collecting ongoing data on specific products, where registries are managed by pharmaceutical companies or national medical agencies, such as the Zolgensma® registry required by the Federal Joint Committee (G-BA) in Germany.9

Alternatively, novel pricing and payment models can be used to facilitate access while managing payer uncertainty. Such is the case with bluebird bio’s Zynteglo® instalment payment plan over five years, where payers only continue to pay the instalments if the beta thalassemia patient continues to respond successfully to treatment.10

Addressing budget impact through novel access and payment models

One of the key challenges for payers and budget holders is assessing not only the extent of benefit but also affordability. This is particularly an issue as curative cell and gene treatments would lead to a direct budget impact at the time of provision, while patients, payers and society at large would reap the benefits over time. This has triggered a debate on the need to develop novel access and payment models that distribute the impact on the budget holder across several years. Payments can also be linked to outcomes to address clinical uncertainties, for instance in outcomes-based contracts in the US and payment-by-results agreements in Europe.

stack of coins and a bottle of pills balancing at either end of a seesaw - idea of budget for/cost of medicines

While individual rare diseases are uncommon and often not considered by payers to have large budget impact, the combined impact of all 5,000 to 8,000 rare diseases is significant. As more potentially curative cell and gene therapies reach the market for a greater number of rare diseases, and potentially more prevalent ones, the budget impact will be considerable. A pushback on prices is already evident with current gene therapies for rare diseases, including Luxturna®, Zolgensma® and Zynteglo®.11-13 Novel payment models, including annuity-based and subscription payments that spread the cost over time or create certainty of the cost expected, can mitigate affordability concerns, but can be resource-intensive to establish and maintain – and require a level of infrastructure which may not be present in all countries.14,15

Conclusions and implications

The advent of potentially curative cell and gene therapies poses significant disruption for healthcare systems. Implications must be considered to ensure that patients, HCPs and wider communities can prosper from the benefits of these therapies. Additionally, there will be significant adjustments to current healthcare systems affecting diagnosis, treatment expertise and infrastructure, value assessment and pricing and market access. Over the next few years, we expect the following issues to have implications for several healthcare stakeholders:

Healthcare disruption

Extent of disruption

Stakeholder implications

Dealing with uncertainty and importance of data and registries

Very High

It is critical that payers develop rules for RWD consideration and collection to curtail uncertainty around curative therapy durability. The establishment of a registry in some markets may be a condition for cell and gene therapy access at launch.

Addressing budget impact through novel payment model

Very High

Budget impact concerns may lead payers and manufacturers to develop novel access and payment models that allow for the spread of payment and impact on the budget holder across many years and as patient outcomes are realised.

Appropriate assessment of value


HTA bodies and payers will need to take a longer-term, broader-based, and more flexible approach as the long-term health and indirect benefits of curative therapies continue to be understood and tested.

Shifting role of primary and secondary settings


Specialised nature of curative treatments will lead to a clustering of care expertise and infrastructure needed for CoEs, where multidisciplinary teams provide integrated care. Primary care may require a shift in use towards other patients or possibly disease areas.

Building an appropriate hospital infrastructure


Extensive support for building hospital infrastructure for preparation, delivery, and administration of curative treatments will be required in dedicated centres or integrated within existing hospitals.

Need for earlier and targeted diagnosis


To realise the full benefits of curative treatments, patients need to be diagnosed early in life, requiring continuous support and broader access to new-born screening in genetic disease areas.

Need for new healthcare expertise


HCPs involved in the current care process will either need retraining or shift to serving patient populations not targeted through gene and cell therapies.

Role of cross-border care


Availability of many curative cell and gene treatments will require a renewed effort to clearly determine regulation attached to provision and reimbursement for cross-border care, given treatment may be provided only in select centres.

About the Authors

Artes Haderi is a Principal within the London office of the Life Sciences Practice at Charles River Associates (CRA). She specialises in public health and pharmaceutical policy and has considerable experience providing analytical solutions to biopharma companies and trade associations.

Anna Hillel is a Consulting Associate within the Boston office of the Life Sciences Practice at CRA. She focuses on pricing and market access engagements, with experience across US and EU.

Rebecca Steele is an Associate within the London office of the Life Sciences Practice at CRA. She works across strategy and policy consulting, with experience in rare diseases and the launch of gene therapies.

The views expressed herein are the authors’ and not those of CRA or any of the organisations with which the authors are affiliated. The authors wish to acknowledge the contributions of Lev Gerlovin and Neil Turner to this article.


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