Advances and challenges for gene therapies in Brazil

Brazil, the most populous country in Latin America, has a public Unified Health System (SUS) that constitutionally provides free healthcare to over 200 million people. Advanced Therapy Medicinal Products (ATMP) have revolutionized medicine, offering curative treatments for some diseases. The Lancet Regional Health—Americas article “Clinical trials to gene therapy development and production in Brazil: a review” by Saute et al.¹ examines the state of gene therapy in Brazil, highlighting the progress made and challenges that remain. This commentary discusses its significance for clinicians and policymakers, emphasizing its implications for clinical practice, healthcare systems, and gene therapy in low-to middle-income countries (LMICs).

For clinicians, this paper serves as a valuable resource on gene therapy advancements in Brazil. It details ongoing clinical trials, approved gene therapy products (GTPs), and the regulatory framework governing their use. Brazil has made significant progress in gene therapy, particularly in gene replacement and CAR-T cells, even though ATMPs were developed by multinational pharma companies. Despite the approval of several GTPs by ANVISA (Brazil's National Health Surveillance Agency), their incorporation into the SUS remains limited² due to high costs and the complex reimbursement models required to make them financially viable. The paper also highlights that Brazil ranks 12th globally in active gene therapy trials, mainly focusing on monogenic diseases and cancers. It also provides a detailed list of ongoing trials, which can serve as a reference for clinicians seeking to explore new treatment options.

For policymakers, this paper highlights regulatory and economic challenges of implementing gene therapy in a resource-constrained setting. Brazil's regulatory framework has evolved to accommodate ATMPs,² ensuring patient safety and efficacy. However, significant gaps remain, particularly in terms of pricing and reimbursement. The high cost of gene therapies hinders their widespread adoption, especially within the SUS, which serves most of Brazil's population. A recent publication by Vianna et al.³ estimates that incorporating 15 ATMPs, already approved in different countries, would compromise between 3.7 and 7.3% of the total Ministry of Health (MoH) budget for 2024. This underscores the need for innovative reimbursement models, such as managed entry agreements, which allow for payment in instalments based on patient outcomes. To offset high costs, fostering a national ecosystem for gene therapy development and production is crucial. Brazil has made significant investments in this area, with public funding initiatives aimed at promoting research and innovation.⁴ However, more needs to be done to ensure the sustainability of these efforts. Policymakers must prioritize the development of local manufacturing capabilities, particularly for viral vectors, essential for gene therapy production. Reducing reliance on imported vectors can significantly lower the costs and improve access.

This paper positions Brazil as a potential leader in gene therapy within Latin America and among BRICS nations. Brazil's modern regulatory framework, scientific capacity, and research infrastructure provide a strong foundation for advancing gene therapy. The country's ability to conduct clinical trials and produce CAR-T cells locally, as demonstrated by the University of São Paulo in Ribeirão Preto, highlights its potential to become a hub for gene therapy in the region. However, the paper also highlights the need for international collaboration and knowledge sharing. Brazil can learn from other countries experiences, such as China and India, which have developed gene therapies at lower costs. For example, India's affordable CAR-T cell production provides a model for Brazil.⁵ By fostering partnerships with other countries and leveraging its existing infrastructure, Brazil can accelerate the development and adoption of gene therapies.

The ethical and social implications of gene therapy, particularly regarding access and equity, are also discussed. The high cost of GTPs raises affordability concerns, especially in a country with significant socioeconomic disparities. Policymakers must ensure that gene therapies are available to all patients, regardless of their ability to pay. In that regard, the MoH has provided significant funding for technology transfer agreements between Caring Cross and Fiocruz for entiviral vector production in Biomanguinhos for all Latin American countries.⁶ Point-of-care CAR-T cell production may reduce the cost by 10-fold compared to current commercial products.⁶ Equally important are the MoH-sponsored tech transfer agreements between Gemmabio and Fiocruz,⁷ which will allow the global production of adeno-associated viral vectors for in vivo gene replacement therapies for rare diseases at a fraction of commercial costs. The role of patient advocacy groups is also highlighted as a critical factor in driving the adoption of gene therapies. Advocacy groups were instrumental for securing reimbursement for Zolgensma® within the SUS, demonstrating the power of patient voices in shaping health policy. Policymakers should engage with these groups to incorporate patient perspectives in decision-making.

The paper concludes with a call to action for Brazil to build a sustainable gene therapy ecosystem, through continued investment in research and development, as well as a supportive regulatory and economic environment. Policymakers must also prioritize workforce training to ensure that Brazil has the skilled professionals needed to advance gene therapy. It also emphasizes the importance of real-world data collection and monitoring to assess the long-term safety and efficacy. This is particularly important given the uncertainty surrounding the durability of these treatments and potential for adverse effects. By establishing national registries and fostering international collaboration, Brazil can contribute to the global body of knowledge on gene therapy and improve patient outcomes.

In summary, this paper comprehensively reviews the current state of gene therapy in Brazil, acknowledging the progress made and persistent challenges. These challenges are not exclusive to Brazil or LMICs but also affect high income countries. By addressing these challenges and fostering a sustainable ecosystem for gene therapy, Brazil can emerge as a leader in Latin America and on the global stage.

Contributors

ACCC and ABC wrote and reviewed the manuscript.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the author(s) used Grammarly in order to improve language and readability. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Declaration of interests

The authors have no relevant conflicts of interest to declare.