Gene therapy can make a real impact on global health but we need equitable access, say experts

This article is brought to you thanks to the collaboration of The European Sting with the World Economic Forum.

Author: Kevin Doxzen, Hoffmann Fellow, Precision Medicine and Emerging Biotechnologies, World Economic Forum

• The development of new gene therapies designed to treat or cure a range of diseases is rising exponentially.
• Access remains an issue, especially in low- and middle-income countries (LMICs) where disease burden is highest.
• Five clinical experts across LMICs explain what steps need to be taken to realize the potential of gene therapies globally.

Low- and middle-income countries (LMICs) can and should play a leading role in dictating the future of the world’s most advanced healthcare technologies, according to the World Economic Forum’s Accelerating Global Access to Gene Therapies: Case Studies from Low- and Middle-Income Countries white paper.

Gene therapy is at the forefront of modern medicine. By making precise changes to the human genome, these sophisticated technologies can potentially lead to one-time lifelong cures for infectious and non-communicable diseases (e.g. HIV, sickle cell disease) that affect tens of millions of people around the globe, most of whom live in LMICs. However, too often the benefits of advanced healthcare technologies remain restricted to high-income countries (HICs), a reality that could happen to gene therapies.

The narrative that new healthcare technologies are unsuitable for LMICs is a long-standing rationale for excluding a majority of the world from the benefits of modern medicine. Without concerted efforts to build gene therapy capacity in LMICs, the global health divide will continue to widen.

The gene therapy industry is in its infancy, but early clinical successes and substantial funding have generated enormous momentum. This is an ideal moment for LMICs to enter the global market, prioritizing the needs of communities carrying the highest disease burdens.

We asked five clinical researchers from LMICs, who are all co-authors on the recent white paper, what innovations on the ground and changes at policy-level need to happen for gene therapy to make a real impact on global health.

‘Perform R&D where target diseases are prevalent’

Dr. Cissy Kityo Mutuluza, Executive Director, Joint Clinical Research Centre, Uganda

Although gene therapy has the potential to treat or even cure life-limiting diseases and infections, the full impact will only be realized if we deliver it for the benefit of all people, instead of fueling more health inequity between and within countries.

An essential first step towards maximizing the global impact of gene therapies is to build research and development (R&D) capacity in LMICs. Current gene therapy R&D has mainly excluded LMICs, instead centering pre-clinical and clinical work in HICs. Gene therapy R&D needs to be performed in regions where target diseases are prevalent to ensure that these therapies are safe and effective for those populations. Manufacturing technologies and healthcare infrastructure, which are the cost drivers for gene therapy products in HICs, need to be replaced with innovative and simplified platforms and workflows that bring down costs and are functional and cost-effective within LMIC health systems.

As for policy and regulation, individual countries must establish gene therapy frameworks that enable R&D. The construction of such frameworks should be guided by recommendations from the World Health Organization, emphasizing safety, effectiveness and ethics.

A critical component in effective global health interventions is community outreach. Treatment acceptability is essential for future clinical trials, thus it is important for scientists and clinicians to be clear about the risks and benefits of gene therapies. Communication and education activities should be made accessible to a broad range of stakeholders. Gene therapy and gene editing technologies are complex and it can be difficult for the public to understand their possible benefits or side effects. However, patient and public support is critical for the successful adoption of any new technology.

‘Leverage pandemic infrastructure and policies’

Professor Johnny Mahlangu, University of the Witwatersrand, South Africa

The ongoing COVID-19 pandemic is accelerating innovation, implementation and acceptance of molecular therapeutics (e.g. mRNA vaccines) globally. As a result, there is escalating interest in developing molecular interventions for many other conditions, such as gene therapies for genetic diseases. Strategically leveraging infrastructure that is being developed for molecular therapeutics will be critical in manufacturing, testing, and delivering gene therapies across diverse settings. Three critical areas of consideration include:

• Repurposing manufacturing infrastructure developed during the pandemic to produce gene therapies. This approach will lower costs and accelerate implementation by maximizing use of existing facilities and workforce.
• Extending the current national policies governing molecular therapies, which were rapidly developed during the COVID-19 pandemic, to include gene therapies. Where gene therapy policies do not exist, governments should create accelerated pathways to efficiently evaluate and approve these advanced medicines.
• Educating patients, healthcare providers and funders on the value and impact of treating lifelong genetic diseases with gene therapies. This education should include upskilling healthcare providers to be familiar with gene therapy-specific processes, including safe product handling, treatment infusion and patient monitoring post procedure.

Health and healthcare

How is the World Economic Forum bringing data-driven healthcare to life?

The application of “precision medicine” to save and improve lives relies on good-quality, easily-accessible data on everything from our DNA to lifestyle and environmental factors. The opposite to a one-size-fits-all healthcare system, it has vast, untapped potential to transform the treatment and prediction of rare diseases—and disease in general.

But there is no global governance framework for such data and no common data portal. This is a problem that contributes to the premature deaths of hundreds of millions of rare-disease patients worldwide.

The World Economic Forum’s Breaking Barriers to Health Data Governance initiative is focused on creating, testing and growing a framework to support effective and responsible access – across borders – to sensitive health data for the treatment and diagnosis of rare diseases.

The data will be shared via a “federated data system”: a decentralized approach that allows different institutions to access each other’s data without that data ever leaving the organization it originated from. This is done via an application programming interface and strikes a balance between simply pooling data (posing security concerns) and limiting access completely.

The project is a collaboration between entities in the UK (Genomics England), Australia (Australian Genomics Health Alliance), Canada (Genomics4RD), and the US (Intermountain Healthcare).

‘Localize manufacturing to lower costs’

Professor Vikram Mathews, Christian Medical College, Vellore, India

Gene therapy is on course to revolutionize medical care for several conditions. The hope is that gene therapy will be a one-time curative therapeutic intervention for diseases ranging from inherited hemoglobinopathies, such as sickle cell disease and thalassemia, to acquired diseases such as HIV.

A primary challenge limiting access to these life-saving therapies is their astronomical costs, making them inaccessible even in developed countries where most gene therapies have originated. Due to economic challenges, there is often a mismatch between regions in the world where development and clinical research happens versus regions in the world where the incidence of the disease target is the highest. Classic examples of these are sickle cell disease and HIV – with the highest incidence rates in Africa.

Moving the manufacturing of gene therapy products to local regions and “point of care” settings (within hospitals) are strategies that can both significantly reduce the cost of these products and improve accessibility. Additionally, current gene therapy approaches use expensive ex vivo procedures that require removal of a patient’s cells from their body. Instead, researchers must develop novel in vivo methods that simplify the procedure to a single injection directly into the patient, saving time and money.

‘Multilevel approach to research strengthening’

Professor Julie Makani, Muhimbili University of Health and Allied Sciences, Tanzania

In order for gene therapy to have an impact on global health, changes in innovation and policy must occur at several levels: individual, institutional, national, continental and global.

At the individual level, patients and personnel are the primary focal points. Taking a patient-centered approach will ensure that the community is involved in research and will have a say in receiving a particular health intervention when it is available. For personnel working in areas pertinent to gene therapy including healthcare, research and education, there is a need to increase knowledge and to change perspectives regarding the advancements and achievements made within the field of gene therapy.

At the national, continental and global levels, genomic research is catalyzed by strategic partnerships and often occur in Centers of Excellence (CoE). Many countries in Africa have established CoEs in academic settings, which integrate health and science programmes. These innovative environments help maximize resources (physical and human) and provide settings that facilitate research and translation of research findings to health interventions to be done contemporaneously, in the appropriate population and geographical region.

At the policy-level, investments in global health and research in gene therapy must change. This can be done in three ways: direct investment to institutions in Africa; increase in the level of investment through funding partnerships; and recognition that the duration of investment needs to be longer than the normal funding cycles of three to five years.

‘Harmonize regulation across countries’

Professor Suradej Hongeng, Mahidol University, Thailand

Gene therapy has received global attention over the last few years, recognition that continues to grow with each new clinical success. The field is constantly evolving, with disruptive innovation across public and private sectors. However, access to these life-saving treatments remain restricted due to a number of technical and policy challenges.

First, researchers must continue to develop cost-effective ways to administer gene therapies into patients, an area of R&D where the private sector can play an important role. Yet many LMICs have weak ecosystems to support the emergence of new companies or entice collaborations with multinational companies. Stronger private sector involvement will be critical for penetration into emerging markets.

Second, the unique nature of these personalized treatments makes them difficult to regulate within traditional frameworks, meaning that agencies must update current policies and regulations. As regulation evolves, it must also converge with the frameworks of other countries. This will make it easier for companies to navigate regulations and interact with agencies when performing clinical trials or bringing a therapy to multiple markets.