Gene Therapies: A Wave is Coming

The field of advanced cell and gene therapies is growing rapidly, with 23 new cell and gene therapies set to be approved in 2023 in the United States and European Union. These promising therapies mark a radical shift from traditional treatment modalities, addressing the underlying genetic causes of disease rather than merely treating symptoms. However, to harness their potential effectively, there is a need for innovation and adaptation that extends throughout the entire health sector. The impressive pace of progress in gene therapies therefore raises an important question for policy makers: are our health systems adequately prepared?

To stimulate a global conversation about the readiness of health systems to integrate and deliver these transformative treatments, ­­­the London School of Economics (LSE) in collaboration with Novartis, hosted an event: "Gene Therapies: A Wave is Coming – Are Health Systems Ready." Coinciding with the 76th World Health Assembly (WHA) in Geneva, this event brought together a stellar panel of experts from diverse fields including health systems financing and development, patient organisations and industry. Past WHA resolutions and World Health Organization (WHO) initiatives have underscored the potential of gene therapies and the need for regulation to keep up with the pace of technological change^1,2,3. But action is also needed at the level of individual health systems to ensure that they are ready and able to adopt and utilise these therapies in a sustainable manner. Our event explored the question of what needs to happen to ensure that they are not perceived as unattainable to all but a few in wealthy countries.

Professor Rifat Atun, Professor of Global Health Systems at Harvard University, set the context in his keynote address, highlighting the sobering reality of rare genetic diseases. Approximately 80% of rare diseases are genetic in origin, 50% affect children, and an estimated 10-30% of infant mortality in low- and middle-income countries (LMICs) are due to rare diseases. Professor Atun's presentation was a meaningful reminder of the significant burden that rare genetic diseases place on individuals, families, and health systems. These diseases, often life-threatening or life-limiting, cause significant suffering and hardship. The emotional, physical, and financial toll on patients and their families can be immense. Furthermore, the broader societal and economic impacts of these diseases are substantial, with health systems often struggling to provide effective and affordable treatments.

Recognising the scope of the challenge, the conversation then moved to the possibilities offered by gene therapies. Gene therapies address the underlying genetic cause of a disease, and offer the potential to halt disease progression or even cure the disease altogether with a single course of treatment. The pace of research is rapid, and the next decade is expected to bring new gene therapies for a wide variety of diseases currently lacking effective treatment, with over 2000 gene therapies currently undergoing clinical trials. However, despite substantial levels of need, access to therapies and cell and gene therapies remains limited, particularly in lower- and middle-income countries. Professor Atun emphasised that implementing them equitably and effectively requires health system innovation. This includes innovation in organisation, financing and regulation, the development of the required workforce and infrastructure, as well as adjustments to the health system delivery model itself.

The road to effective treatment of rare diseases begins with swift diagnosis, but this can often be a complex and lengthy process, involving multiple specialists and numerous tests. Misdiagnosis is common, and all too often patients face years of uncertainty before receiving an accurate diagnosis. Such delays have serious consequences, leading to irreversible disease progression, worse outcomes for patients, and substantially increasing healthcare costs as a result.

This line of discussion brought us to the critical role of newborn screening programs, which test for serious diseases occurring in infancy, in ensuring equitable access to early diagnosis and effective treatment. Joshi Venugopal, General Manager and Head of Europe at Novartis Gene Therapies, highlighted the progress in that has been made in the development and implementation of more effective diagnostic tools and strategies. However, he also noted that these screening programs are far from universally available, leaving many potential patients undiagnosed and untreated. First offering the counterpoint of concerns about declining global birth rates, Joshi Venugopal probed the audience by asking:

"But are we doing enough to save the children who are already born? And can we do a better job in diagnosing these genetic condition and treating them early, so that these children have a great life?"

The experience of Dr Nicole Gusset, CEO and President of SMA Europe, brought to the forefront the human impact of genetic diseases and the transformative potential of gene therapies. Her work with Spinal Muscular Atrophy (SMA) showcased the enormous strides made in gene therapy treatments and underscored the urgent need for broader access to newborn screening to improve early diagnosis and intervention and to these new innovative medicines. SMA is a rare neuromuscular disorder characterised by loss of motor neurons and progressive muscle wasting. Many children with SMA, if untreated, do not survive past the age of 2 due to respiratory failure. Recent advances in medicines including gene therapy have offered renewed hope for patients and their families, and over 3,000 members of the SMA community have received gene therapy treatment, particularly the younger members of the community. However, newborn screening for SMA is available in just a few countries worldwide, and even where it is available, it is not always included in standard screening panels. This is the case in countries as diverse as Switzerland and Tanzania – underlining the distance yet to travel in high- and low-income countries alike.  

The panel next reflected on how gene therapies challenge established healthcare financing and service delivery models. Existing models are orientated towards conventional therapies for chronic diseases, which manage symptoms over an extended period. By contrast, gene therapies often involve a single-dose administration or a short-course duration and address the root cause of the disease, in many cases with cure as a result. Professor Atun further explained that ­­­­­gene therapies can be likened to preventative interventions, such as immunisation, in terms of the benefits they can bring. However, there are countries where gene therapy treatment is not reimbursed. For this reason, families face significant financial barriers to access, with some resorting to crowdfunding to avoid incurring catastrophic health expenditure.

Gene therapies present a financial conundrum for health systems orientated towards chronic diseases. Unlike many conventional therapies, the majority of costs of delivering gene therapies are incurred upfront. While these costs are often higher per cycle of treatment than conventional therapies, the benefits accrue over a patient's lifetime. Existing financing models and annual budget cycles are ill-suited to accounting for fact that gene therapies may be relatively cost effective over the long term despite a high initial budget impact. As Professor Atun noted:

"There is complete misalignment between the budget impact of the intervention,
the costs that are accrued without the intervention, and the benefits that can
be realised with an intervention"

Adequate funding and financing models that recognise the specific characteristics of gene therapies are therefore critical. Professor Atun noted how innovative approaches, such as performance or outcome-based schemes that share risk between the payer, provider, and manufacturer, subscription models which spread payments over time, expanded risk pools and reinsurance models offer potential solutions to this challenge.

Even where finance is available, a lack of infrastructure and expertise for early diagnosis, treatment and post-treatment monitoring can hinder the safe and effective implementation of these therapies. These shortcomings underscored the need for policy commitment and investment across the continuum of care, from screening to diagnosis to treatment and beyond. Farid Fezoua, Global Director of Health & Education at the International Finance Corporation (IFC), emphasised that strong health systems are a prerequisite for deploying innovative therapies like gene therapies, which bring with them an additional degree of complexity. Communication and training are needed across national and sub-national healthcare networks to ensure that the necessary skills are in place for referral, diagnosis, treatment and follow up, and that guidelines – including for patient counselling – are implemented consistently. It is also imperative that genomics databases be expanded to include better representation of diverse populations. Without that, gene therapies will be unable to benefit everyone and could worsen health inequities.

The discussion then turned to the importance of partnerships in the innovation needed to expand access to gene therapies. Farid Fezoua noted how cross-sectoral partnerships are crucial in addressing the challenges in integrating gene therapies into health systems in low- and middle-income countries. The COVID-19 pandemic demonstrated the potential of partnerships – among development finance institutions, public and private healthcare providers, governments, and non-governmental organizations – to accelerate the development and deployment of innovative solutions to improve health, for example, efforts underway to localise manufacture of vaccines in Africa. Mr Fezoua highlighted the importance of building on these lessons to ensure that gene therapies can be effectively and equitably implemented:

"The COVID-19 pandemic opened up doors in the partnership space to implement novel technologies in LMICs. The private sector, governments, and other stakeholders need to collaborate to create the right enabling environment for innovation and deployment in genomics and gene therapies."

Given the challenges involved, the need for collaboration also extends to the stewards of health systems, who must be equipped with the tools to plan for the broader health system innovations necessary and ensure that the regulatory landscape supports them. Tay Salimullah, Vice President and Global Head Value & Access at Novartis Gene Therapies, shared the progress being made to scale and democratise access to cell and gene therapies worldwide. Scaling advanced therapies beyond wealthy countries requires addressing specific challenges early, such as healthcare system infrastructure, regulatory, legal frameworks, affordability and patient identification and follow-up. Tay reinforced:

“We are dealing with 21st century medicines within healthcare systems that
were designed for chronic therapies, requiring a whole new level of co-creation, convergence and cooperation”.

WHO is playing a leading role in this effort, publishing a draft consideration on regulatory convergence of cell and gene therapy products. WHO is also working with Uganda to develop a model framework that can be used by other LMICs to facilitate the integration of gene therapies into health systems.

Building on the theme of collaboration, Nicole Gusset offered a powerful summation of the importance of shared responsibility in harnessing the potential of gene therapies:

"We must find a way to foster research and push the boundaries to pursue innovation.
At the same time, we must equitably provide access. All stakeholders must embrace
the responsibility that comes with innovation and new technology. We need multidisciplinary and international teams to share the tasks, knowledge, and results.
We must work together to bring this incoming wave of gene therapies to all so that
no one is left behind."

With this goal in mind, the event marked the first step in a longer-term initiative. LSE has recently launched a partnership with Novartis, co-led by Professors Elias Mossialos and Rifat Atun, to develop a policy tool to assess health system readiness for sustainable adoption and utilisation of gene therapies. The plan is to apply this tool in different regions across the world with varying levels of health system readiness, to identify concrete steps needed, and build a community of thought and action to share knowledge on best practices. Importantly, the initiative aims to create a platform to enable health system stakeholders in LMICs to identify challenges and develop solutions. Given that the burden of genetic diseases falls disproportionately on people in countries whose health systems have fewer resources, the inclusivity of such initiatives is vital.

The event concluded on a positive note: while the challenges posed by gene therapies are significant, they are not insurmountable. With continued research, collaboration, and innovation, we can work towards a future where these therapies are accessible and beneficial to all who need them. ­­

A special thank you to our speakers:

• Professor Rifat Atun, Professor of Global Health Systems and Director of the Health Systems Innovation Lab at Harvard University
• Dr Nicole Gusset, CEO and President of SMA Europe
• Mr Farid Fezoua, Global Director Health & Education at the International Finance Corporation (IFC)
• Mr Joshi Venugopal, General Manager and Head of Europe at Novartis Gene Therapies
• Mr Tay Salimullah, Vice President, Global Head Value & Access at Novartis Gene Therapies

Gene Therapies: A Wave is Coming - Are Health Systems Ready?