For three years in Poland, patients with spinal muscular atrophy (SMA) had access to effective nusinersen therapy under the B102 drug program. How is it implemented?
The nusinersen treatment program for patients with SMA has from the beginning been broadly open to all patients with SMA, regardless of age, condition, disease form and other factors that alter its course, such as the number of copies of the SMN2 gene. In the first months of implementation of the program, more than 250 patients were qualified for treatment every three months, as it included not only newly diagnosed patients, but also those who had suffered from the disease for a long time and waited for the first treatment option. The program currently treats more than 800 patients in more than 30 hospitals in Poland. Newly registered patients are increasingly being diagnosed as neonatal patients, as part of a newborn screening programme.
Is the treatment effective in all patients, regardless of the stage of the disease?
The program has a clear definition of the effectiveness of treatment: it is at least inhibiting the progression of the disease, it is measured on special scales. So far, no patient has been excluded from treatment due to the fact that the treatment was ineffectiveAnd the Which means that at least all of them have been stabilized. As much as about 90 percent. Patients showed an improvement in their test score on scales assessing kinetic fitness. One hundred patients were excluded from the program primarily because of the choice of another treatment (clinical trial, early access programme). Patients whose treatment was very difficult due to the method of drug administration – lumbar punctures, were excluded in a smaller proportion. It can be very complicated for patients with advanced scoliosis, a common symptom of spinal muscular atrophy.
Is the treatment as widely available in other European countries as in Poland?
The availability of spinal muscular atrophy treatment in European countries varies slightly, but most often it gets better. Adult patients, who do not receive treatment in all countries, experience the greatest difficulties. It should also be noted that in an increasing number of countries, all three SMA approved drugs are available, not just nusinersen.
Why is the drug taken at a fixed dose and does not increase with weight gain?
In fact, nusinersen is given as a fixed dose of 12 mg. However, a clinical trial is underway to evaluate the efficacy and safety of the higher dose. The administration of a fixed dose is due primarily to the biological conditions of the cells on which the drug acts, ie the motoneurons in the spinal cord. These are cells that do not increase in number as the body grows after birth. As a result of this disease, these cells die prematurely. Administration of nusinersen is intended to protect the motor neurons of the spinal cord from premature death.
How has access to the Newborn Treatment and Screening Program for SMA changed the perspective on treating patients in our country?
Poland is the only country where screening of newborns for SMA is common and is performed with public funds. Similar programs exist in an increasing number of countries, but they are often limited, pilot, or funded from other sources. Screening programs identify SMA in most patients before disease onset. The treatment started at this stage gives a great opportunity to protect the patient from the appearance of symptoms, and thus creates an opportunity for the proper motor development of the child. Even if symptoms do occur, they are milder and do not lead to significant disability or serious complications of the disease, including respiratory failure. Let us recall that before the era of treatment, the most common early form of SMA was associated with a risk of death or the need for mechanical ventilation in more than 90% of patients. Sick before the age of two.
What do NURTURE clinical trials say about administering the drug before symptoms of SMA appear?
Clinical trials, including the NURTURE study in which children were given nusinersen before symptoms appeared For the first time, it is possible to prevent symptoms of SMA and ensure that your child develops normally. In this study, children received the treatment from about 20 days of age. Currently, more than 90 percent. Of them walking with support, more than 80 per cent. They obtained the maximum possible score on the CHOP INTEND scale. In the nusinersen treatment program in Poland, children diagnosed with a presymptomatic stage of the disease receive the drug even earlier, on the 15th and 16th days. day of life. The results are observed in it is still early days, since only a few months ago the newborn screening program covered the whole of Poland, but it is already clear that the vast majority of children develop according to the norm.
How does access to nusinersen treatment affect the outlook on the lives of patients and their relatives?
Treatment, especially available to patients in the pre-symptomatic stage of the disease, is changing the perception of SMA as a highly serious, progressive, and often fatal disease. Nowadays, it is avoidable, and almost all children who are treated early have a chance to live without any symptoms of the disease. In the normal course of spinal muscular atrophy, most patients require constant care from early childhood due to the inability to move, eat independently and, in severe cases, stop breathing. Right now, we’re talking to parents of newly diagnosed babies primarily about treatment, not this life-threatening complication, ventilator, tube feeding, or PEG.
In June, for the first time, data on treatment with nusinersen in a pediatric group in Poland appeared in the European Journal of Pediatric Neurology. Please discuss these results.
We summarized the results of nusinersen treatment in Poland in 298 children who received the drug for at least 1 year. For this reason, this analysis does not include children with presymptomatic therapy – before the introduction of the newborn screening program, we practically did not have such patients; There have been several younger siblings with SMA who were diagnosed before birth. Children with spinal muscular atrophy type 1, the most severe form of the disease, and children in the advanced stages of the disease are dominant. Despite these factors that can significantly reduce the effectiveness of treatment, we found a significant average improvement on the CHOP INTEND scale – up to 8.9 points. No patient has discontinued treatment due to its ineffectiveness. The best results were obtained in younger children and patients of a shorter period, ie in the early stages of symptomatic development.
Does nusinersen compensation open the way for other therapies in the treatment of rare diseases?
In fact, the SMA treatment program has completely changed the prognosis for this disease. We emphasize that not only the effectiveness of the drug is important, but also its availability and, above all, early diagnosis. This is ensured by a screening program and extensive educational activities that increase awareness and knowledge about SMA, which also allows early diagnosis of symptomatic patients, who are not included in screening tests, or those whose mutation type is not detected by screening. By the availability of the drug, I mean not only the reimbursement of its costs, but also the participation in the treatment of many hospitals in Poland, and the dedication of the medical staff who do everything possible to ensure that the patient with SMA does not wait for treatment. . It is worth noting that both the clinical tests and the screening program were preceded by arduous research aimed at discovering the cause of the disease and describing its natural course accurately. This made it possible to indicate not only the course of treatment, but also to determine measures of its effectiveness. Such research into rare diseases is very difficult, time-consuming and expensive, incl. Because of the small group of patients and the difficulties in statistical studies, but also because of the low interest of pharmaceutical companies. Currently, a large amount of scientific and clinical research is being conducted into rare diseases. I am convinced that the example of SMA will not be isolated and that similar opportunities will also open up for patients with other rare diseases.
Interview with Agnieszka Fedorczyk
a. Doctor Hebb. n med. Katarzyna Kotulska-Jóźwiak
– Head of the coordination team for the treatment of patients with spinal muscular atrophy, Head of the Department of Neurology and Epilepsy at the Monument Institute – Children’s Health Center in Warsaw.
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