They are part of the so-called advanced therapies and are already available in developed countries, where thousands of patients have been treated with surprising results. Despite being considered “the future of medicine” in our country, none of them are available. On World Health Day, national and international experts address the challenges of accessing these treatments that save lives, but are not accessible.
It sounds like science fiction, but it is not. What is certain is that there is a lot of science behind the development of advanced therapies that use genetically modified cells. This type of immunotherapy uses samples extracted from the patient’s own tissues or blood, from which specific types of cells are separated and genetically modified through laboratory processes. Once these cells multiply, they are injected back into the patient as a treatment for a certain disease.
One of these therapies is CAR T cells. Approved by the U.S. Food and Drug Administration (FDA), immune T cells (which are a type of white blood cell) are extracted from patients with certain types of cancer to be reprogrammed in the laboratory. This type of lymphocyte, present in all people, acts naturally against cancer cells. However, cancer cells have the ability to hide from the immune system. When T cells are genetically modified in the laboratory by adding the chimeric antigen receptor (CAR), they are able to recognize and destroy tumor cells more effectively.
The use of this therapy has generated great expectations in the world of medicine, due to its promising results, mainly in acute lymphoblastic leukemia, non-Hodgkin lymphomas and multiple myeloma. Patrick Hanley, MD, Director of the Cellular Therapy Program at Children’s National Hospital in Washington, D.C., explains, “Advanced therapies, such as cell and gene therapies, are often personalized, highly targeted, and potentially curative with a single treatment. In many cases, these advanced therapies have far fewer side effects than traditional chemotherapy and radiation therapy, although they may have unique toxicities that we are still learning to better manage. In the case of CAR T cell therapies for acute lymphocytic leukemia, they offer significant hope to patients who previously had mixed survival chances after an initial relapse.”
Julian Molina is an oncologist at the Mayo Clinic in Ronchester, Minnesota, and is an expert in the treatment of lung cancer, lymphoma, and small bowel and colorectal cancer. During his participation in the Impact of Cellular and Gene Therapies (IMPACT-CGT) Meeting organized by the IMPACT Basal Center of the Universidad de los Andes on March 21 and 22, he addressed the results that advanced therapies offer. “In oncology, what we have always done is use chemotherapy, and today there is very little research into finding new drugs, that is already in the past. The future of oncology, of anticancer treatment, is immunotherapy,” she says.
Based on his experience, the expert affirms that the use of innovative immunotherapies has drastically modified the mortality of some types of cancer. “When you look at the tumors that benefit most from immunotherapy in general, they are, for example, lung cancer, melanoma and kidney cancer. To give you an example: ten years ago, a patient with stage four lung cancer had a survival of 1.5 to 2 years. At this time, we have almost 40% of patients alive and well after 5 years, and this is due to the effect of immunotherapy. When we say cell therapies, we are looking to make immunotherapy more sophisticated, that is, we are not only going to give antibodies, we are going to give the cells that the antibody is trying to activate in the patient’s body directly so that the response is better and longer lasting,” explains Molina.
Developed countries such as the United States already have seven of these immunotherapies approved by the FDA. In Chile, none are available.
The problem of regulation
Doctors and researchers agree that the future of medicine is advanced therapies, hence the research in this area is increasing and Latin America is no exception. During the IMPACT-CGT Meeting, scientists from various countries in the region gave an account of the work they are doing.
Martin Bonamino, a researcher at the National Cancer Institute of Brazil and a member of the Legal and Regulatory Affairs Committee for South and Central America of the International Society for Cellular and Gene Therapy (ISCGT), explains that one of the challenges facing these therapies is whether their effects are replicable in Latin America. “We have to see if the solutions that are being developed in the United States and Europe have the same level of response in our populations, which have a different genetic background,” he says. However, this challenge is not the only one.
The regulation of advanced therapies is one of the problems that scientists and doctors face. In Chile there is still no regulation. Fernando Figueroa, a rheumatologist at the Clínica Universidad de los Andes and coordinator of the Clinical Program at the IMPACT Center, points out that the lack of regulation is an obstacle both to address new developments that are currently occurring around the world and to any form of national or foreign marketing. “The Public Health Institute (ISP) approved in February 2022 a Clinical Guide for conducting clinical studies with biological products. This guide is a step forward in terms of Good Manufacturing Practices and health authorization of production laboratories. It also refers to research products in advanced therapy, despite the fact that in Chile this concept is not defined in the Health Code. This is probably a new opportunity to deploy greater instances of collaboration between researchers and regulatory bodies, as ANVISA has done with great success in Brazil. There is interest and concern from all the actors; new technical guides, products of previously unimaginable effectiveness in full global development. I would say that Chile is facing a challenge to meet in this matter,” he says.
The IMPACT-CGT meeting addressed the work currently being carried out by the ISP through the participation of Carolina Sepúlveda, Head of Advanced Therapies and the Subdepartment of R&D&T and ETASA of ANDID (ISP), who pointed out that they considered the examples of Brazil, South Korea and Japan in terms of regulation and even FDA meetings in the United States have been held, and that the great challenge is to adapt international regulations to local reality.
However, the development of advanced therapies is going faster than the regulations and their absence limits not only the research but also their manufacturing processes and application in patients.
Medicine of the Future only for some?
Asked about the problem that worries them most about making advanced therapies available to patients, experts unanimously declare the costs of these treatments. “The potential of these therapies arouses great expectation and enthusiasm because they are truly personalized, that is, they are manufactured specifically for each patient. They have changed the paradigm of modern medicine. We are talking about high survival rates for patients who previously had few treatment options. The drawback is that we continue to struggle to find ways to pay for the therapies and, in the case of many European countries, they have simply chosen not to offer them. The way therapies are manufactured and supplied is also changing, as decentralized manufacturing is gaining momentum as a way to reduce costs and increase patient access. In places like the Netherlands, these advanced therapies are now manufactured in the hospital pharmacy, rather than at a centralized drug manufacturer. It is early days, but very exciting,” says Hanley.
Although this research has been going on for decades in the United States, high costs are also a problem that has not been resolved and continues to affect thousands of patients. “The cost of producing cells for someone with leukemia or lymphoma alone is around $450,000. To that cost you have to add that these patients will spend an average of 7 days in the hospital and 1 or 2 days in the Intensive Care Unit, with the costs that this has due to the immediate effects of the therapy, plus the fact that they need very close monitoring for a month, which implies that they must stay in the city where we give them the treatment. In economic terms, the costs of a therapy should be around a million dollars. If this therapy is approved by the FDA, the patient must take it through health insurance; if not, they have to be part of a clinical study, which is also very expensive and therefore difficult to finance,” explains Mayo Clinic oncologist Julian Molina.
In Chile, therapies are not approved by the regulatory body, but even if they were, their production costs are another challenge to overcome. A challenge that the IMPACT Basal Center has set out to accept.
Maroun Khoury leads the IMPACT Center, which was born with the main objective of making these treatments accessible and affordable in our country. Although he recognizes that it is a great challenge, during the two years that IMPACT has been running, thanks to funding from the National Agency for Research and Development (ANID) and the collaboration of the University of the Andes, have focused on supporting clinical research through the creation of an academic-based clinical trial coordination unit called CRIO. They have also proposed to actively participate in expert tables with regulatory entities in order to support the development of a regulatory framework that allows providing access to therapies such as CAR T. “We hope to achieve agreements and resolutions to provide therapies to various health institutions. with the capacity to administer the treatment, and co-payment agreements initially with additional health agreements and insurance.”We are also participating in organizations such as Pro Salud Chile, which advocate for innovation in the benefit of patients and people,” he explains.
For Cristina Puig, associate professor at the University of California, Los Angeles (UCLA) and member of the Jonsson Comprehensive Cancer Center (JCCC) and the Broad Stem Cell Research Center (BSRCR) in the United States, advanced therapies “are very new, and challenges are found at all levels, whether it is treatment design, production, clinical management of toxicities associated with these treatments, and the regulatory context. As we accumulate more knowledge in all these areas, clinical translation will become increasingly easier. However, it is encouraging to see the efforts being made to give patients in all countries access to therapies that have already proven to be effective against the treatment of advanced tumors,” she says.
We are no longer talking about science fiction. More than 7,000 patients have been treated in the United States with CAR T cells since 2016. And while the scientific community recognizes that there is still much to investigate, all the evidence points to the fact that in the future these therapies could be great tools to deal with diseases that currently have no effective treatments. How far that future will be in Chile will depend on the advances in regulations that allow for better access and greater financing.