Mario Chiong-Lay, Rosa Pardo and Sergio Lavandero, academics from the University of Chile, of the Faculties of Chemical and Pharmaceutical Sciences, of Medicine and the Clinical Hospital, Tomás Ross' health problem is reviewed, A boy from Ancud whose mother came walking to the capital with the purpose of raising funds for his high-cost treatment. In this text, Experts are looking for “provide information to help clarify doubts about the effectiveness of the drug, its eventual administration in Chile and the costs of gene therapies”.

During the last few weeks, all of Chile has witnessed theHistory of Thomas Ross, his illness and his mother's efforts to get a state-of-the-art drug. In this text we want toprovide information to help clarify doubts about the effectiveness of the drug, its eventual administration in Chile and the costs of gene therapies.

Let's start with the illness that afflicts Thomas, which is known asDuchenne muscular dystrophy (DMD). It is a genetic disorder, Rare, caused by mutations in the person's genetic information, which does not allow us to have aA protein called dystrophin, which is key to the integrity of muscles.Their lack causes progressive destruction and loss of them, which causes people with this disease to have a very low life expectancy and quality of life – between 12 and 21 years old.

Curing this disease has been the goal of various investigations. Today, Thanks to scientific advances, agene therapy, where we can introduce a gene without mutations that replaces the defective gene. However, The dystrophin gene is the largest gene we have in our body, which has made it impossible to achieve a complete replacement. For this reason, A smaller version of the gene and protein has been designed, called microdystrophin, What, while retaining essential parts of normal dystrophin needed to maintain muscle cell stability, It is not identical to the original protein.I.e., This version of the protein does not cure the disease, but it has the potential to transform DMD into a milder, more benign form, very similar to Becker muscular dystrophy (DMB), where quality of life and life expectancy are highest – 40 to 50 years.

To achieve this gene transformation therapy, an adeno-associated virus is used (AAV), which is modified to produce microdystrophin. This virus inserts itself into the genetic material, causing microdystrophin to be produced -express- permanently over time. The question is how long does the effect of gene transformation using this technique last in the body? In theoretical form, Very long time, since the virus is permanently integrated into the genetic material. In this sense, The clinical data we have to date on hemophilia B, disease that uses the same AAV virus, have shown therapeutic efficacy for at least 4 years.

Gene therapy to treat DMD, to which Tomás es Elevidys will be subjected, was approved through the expedited and exceptional pathway by the Food and Drug Administration (FDA) of the U.S. USA. in 2023. Data from the first part of this study established that Elevidys increased the expression of the protein microdystrophin in children with DMD aged 4 to 5 years, but there was only a slight improvement in motor and muscle function in these patients. A second clinical study evaluated a 5-year follow-up, only 4 children with DMD 4 to 5 years of age. Their results showed that gene therapy significantly increased microdystrophin levels in muscle tissues and that this increase persisted for 5 years, but it was not possible to improve the mobility of the participants.This history shows that this gene therapy is not curative, but it slows the progression of DMD.

What should be done to treat Tomás in Chile?

Recently the Minister of Health, Ximena Aguilera, offered Tomás' mother support in case they want to administer the medicine in Chile, indicating that they can help "facilitate the importation, procedures that are done through the Institute of Public Health (ISP), and its administration in a public establishment”.  However, we must remind the Minister, WhatElevidys is not an approved drug in Chile and must be acted upon in accordance with the Ricarte Soto Law (Law 20.850).This slows down the process by mandating the authorization of the ISP and the issuance of a supreme decree for its provisional use. In addition, The protocol of use must be presented, The Informed Consent Form, and a liability insurance policy.

On the other hand, the health center where this medication is administered must be accredited and supervised by the ISP, conforming to standards, requirements and procedures established by law. Additionally, The institution using this medicinal product shall be liable for any damage caused by its administration, even if these are derived from facts or circumstances that could not have been foreseen or avoided according to the state of knowledge of science or technology, existing at the time of the damage. Based on this background, the question arises whether the ministry will be able to efficiently take charge of all these administrative responsibilities?”.

Is Tomás' treatment the most expensive drug in the world?

A third point that has revealed the story of Tomás, are the costs of gene therapies and people's access to them. At last, Elevidys is one of several gene therapies approved by the FDA. Up to 17 new gene therapies are expected to be approved this year. All of these treatments are very expensive, ranging from 2 to 4,$25 million each.

Although it is very necessary to discuss at the level of society the ethical financing of these pathologies in Chile, it is more urgent to approach the problem in a more globalized way, for this reason, a Law on Rare or Rare Diseases (EPOF) is required- that not only ensures access to high-cost drugs, but also to improve the living conditions of all people with EPOF in Chile, which are estimated to be approximately 1,5 million. Si public policies based on scientific evidence are not developed, How long will we continue with the walks to Santiago??

Dr. Mario Chiong-Lay
DRA. Brown Rose
Dr. Sergio Lavandero

Academics of the University of Chile – ACCDiS. Faculties of Chemistry and Pharmaceuticals, Medicine and Clinical Hospital.

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