by The European Medicines Agency (EMA) has just recommended marketing authorization in the European Union for a new therapy to treat adult patients with amyotrophic lateral sclerosis (ALS), a rare and often fatal disease that weakens muscles and causes paralysis. . . Qalsody (tofersen) would be indicated for the treatment of adults with ALS, who have a mutation in the superoxide dismutase 1 (SOD1) gene. This data is relevant, points out Javier Rodríguez de Rivera, Coordinator of the Neuromuscular Diseases Study Group of the Spanish Society of Neurology, “only 1 in every 100 patients.” In patients with amyotrophic lateral sclerosis (ALS), nerve cells in the brain and spinal cord that control voluntary movement gradually deteriorate, causing increasing loss of muscle function and paralysis of voluntary muscles, including the respiratory muscle, which It eventually leads to respiratory failure. Related News report Yes ALS patients pushed to euthanasia Elena Calvo Those affected report that they are pushed to ask for death due to the impossibility of paying for their illness ALS is a devastating disorder. The average survival time with ALS is two to five years. Currently there is no cure and the average life expectancy of patients is two to five years from diagnosis. A reality that around 100,000 Spaniards will have to face throughout their lives, that is, 1 in every 400 people. Currently there is only one drug approved in Spain, riluzole, says Rodríguez de Rivera, a neurologist at the La Paz hospital in Madrid. Approved in 2023, it acts as an inhibitor of glutamate release. International clinical practice guidelines recommend starting treatment with riluzole as soon as possible after diagnosis and maintaining it throughout the progression of the disease. It is estimated that it can prolong life between 6 and 19 months. How does it work? Does this drug really work? this expert asks. «Riluzole works alone by reducing the speed of disease progression by 30%. We are not talking about a spectacular treatment, but we are talking about importance, because nothing else exists. Currently, patients are offered supportive treatment to relieve symptoms of the disease, such as physical, occupational or speech therapy, and respiratory support. However, there is a large unmet medical need for effective therapies that preserve muscle function and prolong the lives of ALS patients. The exact causes of ALS are unknown, but are believed to include genetic and environmental factors. In about 2% of people living with ALS, the condition is caused by a genetic mutation (change) that leads to the production of defective SOD1 enzymes, resulting in the death of nerve cells. Qalsody is an antisense oligonucleotide that binds to the mRNA of the SOD1 gene to reduce the production of the SOD protein. By reducing the amount of the defective SOD1 protein, this drug is expected to improve ALS symptoms. The opinion of the EMA committee for human medicines (CHMP) is based on evidence, including the specific way the medicine works, from the effects observed in an SOD1 animal model, biomarkers and clinical data. There is a medical need for effective therapies that preserve muscle function and prolong the lives of ALS patients. Data were obtained from a 28-week randomized, double-blind, placebo-controlled clinical study in 108 patients aged 23 to 78 years with weakness attributable to ALS and a core laboratory-confirmed SOD-1 gene mutation. The study randomly assigned 108 patients in a 2:1 ratio to receive treatment intracally (via spinal injection) with Qalsody or placebo for 24 weeks. During the study, plasma neurofilament light chain (NfL) was measured as a marker of damage and deterioration of axons (thread-like structures attached to nerve cells that send signals outside the cell). Reductions of approximately 60% in plasma NfL concentrations were observed in patients receiving Qalsody compared to the placebo group, suggesting a reduction in neuronal injury. There was also an improvement in the physical abilities of patients receiving Qalsody compared to study participants receiving placebo, as measured by the standard rating scale known as the ‘ALS Functional Rating Scale-Revised’ (ALSFRS-R). ). ) 1. The CHMP requested the applicant to submit post-authorisation data to better characterize the long-term efficacy and safety of Qalsody, based on a long-term open-label extension study, collaboration with two disease registries and a registry-based observational study. Furthermore, it will be investigated whether the use of this new drug can delay or even prevent the onset of clinically manifest ALS in patients with presymptomatic SOD1 ALS. The most frequently reported side effects were pain, fatigue, pyrexia (fever), arthralgia (joint pain), myalgia (muscle pain), and increased levels of white blood cells and proteins in the cerebrospinal fluid (brain and spinal cord). . . The CHMP consulted patient representatives during the assessment of the benefits and risks of Qalsody to ensure that patients’ needs and perspective are taken into account in the regulatory decision-making process. The opinion by the EMA is an intermediate step in Qalsody’s path towards patient access. It will be sent to the European Commission for a decision on marketing authorization throughout the EU. Once marketing authorization has been granted, decisions on price and reimbursement will be made at the level of each Member State, taking into account the potential role or use of this medicinal product in the context of the national healthcare system of that country. What to do to receive the medication? González de Rivera explains that Spanish patients with ALS can access this treatment through an early access system, with which the hospital can request it from the laboratory to access it for free. However, he points out “the problem is the procedures, which sometimes take months. “We hope they speed up.” Drug discarded In August 2023, the EMA rejected the marketing of Albrioza (Amylyx Pharmaceuticals), a treatment for ALS, considering that it has not been truly proven that this drug slows the progression of this neurological disease. The Canadian health authorities approved Albrioza in 2022, despite not having completed all the research phases. The pressure from patients, who have almost no treatment options, led Canada to justify its decision “due to the few therapeutic options available to ALS patients.” “Now the benefits of Albrioza outweigh the risks,” argued the Canadian Ministry of Health, which has become the first country to authorize it. However, the EMA is concerned that the main study does not convincingly show that Albrioza was effective in delaying the worsening of the disease. Survival data were also unreliable, given the way they were collected and analyzed. ‘It is not entirely clear how Albrioza works, but the two active ingredients, sodium phenylbutyrate and ursodoxycoltaurin, were expected to reduce damage to nerve cells and prevent them from dying. “This was expected to help maintain normal muscle function and delay the worsening of the disease,” the EMA detailed in a statement. In this sense, González de Rivera adds, there really is not enough evidence to approve Albriozola. But, as Adriana Guevara, president of the Spanish Association of Amyotrophic Lateral Sclerosis (adELA), pointed out at that time, “any ALS patient is eager for something to come out, although you have to be cautious and talk to the Spanish specialists and researchers who are very prepared and they are going to advise us.
