Amyotrophic lateral sclerosis (ALS) is a very serious disease that progressively weakens muscles and causes paralysis. Its prognosis is very poor because most patients only survive between two and five years after diagnosis. Any novelty in its treatment is a ray of hope because it can improve the quality of life of those affected and now the European Medicines Agency (EMA) has recommended granting a marketing authorization in the European Union for Qalsody (tofersen), a new therapy indicated for the treatment of adults with ALS who have a mutation in the superoxide dismutase 1 (SOD1) gene.
In people diagnosed with amyotrophic lateral sclerosis, the nerve cells found in the brain and spinal cord that are responsible for voluntary movement progressively degenerate, leading to a loss of muscle functionality and paralysis of voluntary muscles, including respiratory muscles, which ultimately causes respiratory failure.
The exact causes of ALS are unknown, but it is considered that genetic and environmental factors play a role in the disease. In about 2% of affected individuals, ALS is due to a genetic mutation that leads to the production of defective SOD1 enzymes that causes nerve cell death.
How Qualsody works to combat ALS
Qalsody is an antisense oligonucleotide that attaches to the mRNA of the SOD1 gene, with the aim of reducing the production of the SOD1 protein. By reducing the amount of the defective SOD1 protein, this treatment is expected to alleviate the symptoms associated with ALS. Currently, there is only one treatment for ALS (riluzole) authorized in the EU.
“It is true that the therapeutic effects are limited, since intervention on this mechanism, although evident at the molecular level, has fewer effects from a clinical point of view. These moderate effects translate into a slowdown in motor degeneration and respiratory function, with a consequent improvement in the quality of life of patients,” explained David Pozo Pérez, principal investigator of the Cellular and Molecular Neuroimmunology laboratory of the Andalusian Center of Biology. Molecular and Regenerative Medicine (CABIMER) in statements to SMC Spain.
The recommendation of the EMA Committee for Medicinal Products for Human Use (CHMP) is based on a comprehensive analysis of the evidence, including the mechanism of action of the medicine, the effects observed in animal models with SOD1, biomarkers and clinical data, which are collected from a 28-week randomized, double-blind, placebo-controlled clinical study that included 108 patients aged 23 to 78 years with weakness due to ALS and a mutation in the SOD-1 gene confirmed by a central laboratory. .
The study randomized the 108 patients in a 2:1 ratio to receive intrathecal treatment (via spinal injection) with Qalsody or a placebo for 24 weeks. Plasma neurofilament light chain (NfL) was measured during the study as an indicator of damage and deterioration of axons (thread-like structures attached to nerve cells that transmit signals away from the cell). Reductions of approximately 60% in plasma NfL concentrations were observed in patients treated with Qalsody compared to the placebo group, suggesting less neuronal injury.
“The therapeutic effects are moderate and translate into a slowing of motor degeneration and respiratory function, with a consequent improvement in the quality of life of patients”
There was also a numerical improvement in the physical abilities of patients treated with Qalsody compared to study participants receiving placebo, as measured by the standard rating scale known as the ‘ALS Functional Rating Scale–Revised’ (ALSFRS). -R).
The CHMP has requested the manufacturer to provide post-authorisation data to more precisely characterize the long-term efficacy and safety of Qalsody, through a long-term open-label extension study, collaboration with disease registries and an observational study. based on records.
Additionally, it will be explored whether the use of tofersen can delay or prevent the clinical manifestation of ALS in patients with asymptomatic SOD1 ALS. The most frequently reported side effects include pain, fatigue, fever, joint pain (arthralgia), muscle pain (myalgia), and an increase in the levels of white blood cells and proteins in the cerebrospinal fluid (brain and spinal cord). spinal).
“The approval by the EMA (approximately a year after the FDA) of a drug based on ASO technologies (Antisense Oligonucleotide Therapy) against a largely genetic form of ALS, in those patients who present mutations in the SOD1 (superoxide dismutase 1) and that they represent a very limited number of them, is positive news. Among other things, it shows that the set of knowledge that we are acquiring at a molecular level is beginning to be transferred to patients,” said David Pozo.
“It is not a cure for ALS, but it is certainly an important milestone; The disease has been described in medical literature for just over 150 years. And, above all, it may represent one more tool to, in the near future, have combined strategies with different pharmacological approaches for adequate clinical management of ALS,” concludes the expert.
