Access to gene therapy in Latin America: benefits and challenges
MD. MSc. EdM
Marian Rincon Mountain MD
Department of Epidemiology and Biostatistics
Pontifical Javeriana University
Gene therapy consists of the transfer of exogenous genetic material to a patient, to treat a genetically based disease (1). Although the concept had been around long before, research in humans began in 1990, when the first clinical study for the treatment of a rare immunodeficiency was conducted. Progress has been rapid, and since then more than 2,500 studies have been conducted for a wide range of diseases, including not only monogenic genetic defects, but also infectious diseases, complex neurodegenerative disorders, and cancer. It is precisely this last indication that has the largest number of clinical trials (2).
Gene therapy has been studied in severe combined immunodeficiencies, thalassemias, sickle cell anemia, hemophilia, and hereditary vision loss (3). Given the high costs and the necessary technological infrastructure, in Latin America many efforts are needed to promote its advance, and to alleviate the social and financial burden it represents (1).
It is first important to know the real benefits of gene therapy to justify its inclusion. One of its main advantages is its potential to prevent later morbidity, in the long term, with a single treatment. Gene therapy carries a unique cost that, although it may seem high, must be weighed against the sum of morbid events and ongoing care over many years. Advance approvals of different agents for gene therapy have led to interesting discussions about how best to determine their “value” (4). The word value must be understood as a multidimensional concept that must take into account the benefits for the patient (improvement in quality of life and decrease in years lost due to disability), as well as consider the economic impact generated by the disease (and therapy) on health systems, and on the patient's family, social, school or work environment. In any case, research on the subject in the region is scarce, and resources are more limited than in the developed world (1).
Gene therapy promises to offer unique and numerous benefits: these therapies can increase survival, decrease morbidity, and in some cases end disease progression (5). For example, in a phase II clinical study with patients with beta thalassemia who received their own genetically modified stem cells, there was a reduction or elimination of the need for long-term transfusions in all who participated (n = 22) ( 6). Even if the direct cost of a gene therapy is estimated to be equal to the direct costs over the life of the patient, the added benefits of a treatment that only requires one dose and potentially has a long response is a situation that has many benefits by reducing the burden on the health system and on the patient himself. Gene therapy can offer quality-of-life benefits by reducing or eliminating pain, by providing a sense of well-being for patients, and by avoiding their dependence on chronic treatments. However, the durability of these therapies is still theoretical, and it requires time and additional studies to evaluate it (7).
More than other health inventions, scientists, regulators and payers (as well as patients) are required to participate in the mid- and long-term evaluation of the benefits of gene therapy to justify or not subsequent approvals and to consider its financing by health systems. The FDA has recognized that for an innovative technology such as gene therapy, a new regulatory framework needs to be developed. Given that this therapy currently focuses on rare diseases, the FDA is looking for statistical alternatives to perform the evaluation of clinical trials, in order to address the challenges that arise, for example, with small patient samples, and with the use of “intermediate” outcomes (4.8). That is why the FDA is making efforts to validate the ideal outcomes and obtain patient-centered results, to make regulatory decisions that can highlight the relevant benefits for all involved.
As an example, the FDA provided information to clinical investigators to establish a new endpoint for measuring the efficacy of Luxturna, a drug that provides gene therapy to reverse blindness in some conditions (2). The outcomes measured in this study were designed to approximate real-world situations. They suggest that payers should consider trial outcomes as clinically relevant, even if they are not typical measures of efficacy used in other types of treatment (4).
If determining this access from a clinical perspective and determining the value of this technology requires flexible thinking, new forms of financing are also required to cover its high upfront costs. Equitable access for all patients is crucial to emphasize the potential value of these therapies. Stakeholders should continue to develop creative approaches to pricing and reimbursement as these new therapies enter the market (4).
One could say that the preference between long-lasting and potentially curative treatment, rather than a lifetime of chronic disease, or a short life, is easy. However, the people involved in bringing these technologies to market, as well as the payers, must answer fundamental questions to determine the benefit they offer to health systems. Some of these questions are: what are the payment models that have been proposed to pay that amount that patients receive; how to mitigate the burden of upfront costs; what are the policies, legislation and barriers that must be introduced to achieve the implementation of timely payment and reimbursement; how current models of care (and financing) can be expanded or modified to embrace these new technologies. (4)
Among the solutions preferred by payers are results-based contracts that include risk-sharing agreements, in which payment is reduced or eliminated if a patient does not respond to treatment. Contracts could also be based on time-distributed installments and risk packages to provide resources to insurers when the cost of therapy exceeds a predetermined threshold (9).
The outlook in Latin America is not so favorable, since historically funding for research in general has been insufficient and has tended to be erratic. Furthermore, both products and procedures related to gene therapy, especially those directed towards rare diseases, are expensive. To date, the results of clinical studies designed, conducted, and funded by local agencies have rarely been published (1).
About 80% of the human studies come from the United States, United Kingdom, Switzerland, Germany and France, mainly because phase III and IV studies require special industrial support to cover the costs of supplies and logistics, money that probably will not it can be invested for this purpose in Latin America (1). Given the very specific target population this technology is targeting, and the expected high costs, even decision-makers in high-income countries have identified it as a problem, and it is proposed that those costs would have to be reduced so that gene therapy can reach regions like ours (10).
In conclusion, decision makers and payers in Latin America should consider gene therapy as a new therapeutic option for the treatment of various diseases, destined to expand in the near future. However, given the social and economic situation of the region, investment for this technology is difficult in the short term (1). In general, the path to paying for gene therapy is fraught with challenges, including political constraints, different perspectives on the concept of value, and other third-party interests. However, now that the first products are beginning to be approved, it is the responsibility of all stakeholders to take up these challenges and maximize their potential access for the benefit of patients.
1. Linden R, Matte U. A snapshot of gene therapy in Latin America. Genet Mol Biol. 2014; 37 (1 Suppl): 294–8.
2. Anguela XM, High KA. Entering the modern era of gene therapy. Annu Rev Med. 2019; 70: 273–88.
3. High KA, Roncarolo MG. Gene therapy. N Engl J Med. 2019; 381 (5): 455–64.
4. Salzman R, Cook F, Hunt T, Malech HL, Reilly P, Foss-Campbell B, et al. Addressing the value of gene therapy and enhancing patient access to transformative treatments. Mol Ther. 2018; 26 (12): 2717–26.
5. Dreitlein B, Towse A, Watkins J, Paramore C. Developing and paying for gene therapies - can we resolve the conflicts? Value & Outcomes Spotlight. 2018; 4: 31–4.
6. Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, et al. Gene therapy in patients with transfusion-dependent beta-thalassemia. N Engl J Med. 2018; 378 (16): 1479–93.
7. Hampson G, Towse A, Pearson SD, Dreitlein WB, Henshall C. Gene therapy: evidence, value and affordability in the US health care system. J Comp Eff Res. 2018; 7 (1): 15–28.
8. US Food and Drug Administration. Evaluation of devices used with regenerative medicine advanced therapies draft guidance for industry [Internet]. 2019 [cited 2019 Aug 15]. Available from: https://www.fda.gov/%0Adownloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/%0AGuidances/CellularandGeneTherapy/UCM585417.pdf.
9. Ali F, Slocomb T, Werner M. Curative regenerative medicines: preparing health care systems for the coming wave. In Vivo. [Internet]. 2016. [cited 2019 Aug 15].
Available from: https://invivo.pharmaintelligence.informa.com/IV004955/Curative-Regenerative-Medicines-Preparing-Health-Care-Systems-For-The-Coming-Wave.
10. Podhajcer O, Pitossi F, Aguilar-Cordova E. Gene therapy coming of age in Latin America. Mol Ther. 2002; 6 (2): 153–4.