Spinal muscular atrophy (Sma), AIFA gives the go-ahead to extend reimbursement for SMA gene therapy

Spinal muscular atrophy (Sma) It is a rare and serious neuromuscular diseaseas well as the first cause of genetic infant death, characterized by the progressive loss of motor skills, which occurs when it results missing or defective version of a gene necessary to produce an essential protein known as motor neuron survival protein»(Smn).

On the treatment front, the Italian Medicines Agency (AIFA) has recently given the green light to the extension of the reimbursement of onasemnogene abeparvovec, the first gene therapy for SMA, to children with Sma 2 up to 13.5kg and to pre-symptomatic people with 3 copies of the Smn2 gene, thus opening up further treatment perspectives for the community of young patients with spinal muscular atrophy and their families.

The situation in Italy

In Italy About 40-50 children are born every year with spinal muscular atrophy; precisely the lack of Smn protein, which causes the death of the nerves that control the muscles (motoneurons), makes daily gestures such as sitting and standing, and in the most serious cases swallowing and breathing difficult. SMA is a “disease continuum”, with a range of symptoms that can vary in their severity, so much so that different types of SMA can be classified. Among these, SMA type 1, whose symptoms develop at the age of 6 months, and SMA type 2, with symptoms appearing between 6 and 18 months of age, are the most serious.

Extended refundability

From today, with the extension of the reimbursement indications, the first gene therapy approved in Italy, onasemnogene abeparvovec, is also available for patients suffering from spinal muscular atrophy type 2 (Sma2) and for pre-symptomatic patients with 3 copies of Smn2 and up to 13.5 kg. Thus expanding the audience of young patients who will be able to access this treatment, at a time when Neonatal screening, fundamental for the timely diagnosis of the disease, is expanding to more and more Italian regions.

«We welcome the news of the expansion of access to gene therapy that will be made available – declares in this regard Anita Pallara, president ofSMA Families Association – for a greater number of children suffering from spinal muscular atrophy. We know that gene therapy increases its effectiveness and, therefore, improves the patient's response the earlier it is administered. Because of this, as the SMA Families Association we reiterate the importance of newborn screening, which must be extended to all regions in order to guarantee the same right to health throughout the national territory. Alongside screening, we also underline the importance of guaranteeing families the necessary accompaniment in the treatment process and in the subsequent post-treatment follow-up phases, through care by specialized centers across the entire national territory.”

I study

In support of the reimbursement extension, the completion of the phase III SPR1NT studywhich demonstrated how young patients with three copies of the Smn2 backup gene, treated pre-symptomatically, achieved age-appropriate motor milestones, including the ability to stand and walk.

The same study also confirms the importance of neonatal screening for SMA, which is increasing significantly the probability of identifying patients affected by the disease when they are pre-symptomatic, with a significant impact on potential therapeutic outcomes. Making it possible to administer the therapy, in the first days of life, to 95% of children who would have developed, due to the genetic mutation, the most serious forms of the pathology (Sma1 – Sma2 phenotypes).

Motor development almost similar to that of healthy peers

«Early administration of this innovative treatment allows for better results to halt the progression of the disease: prenatal diagnosis, by increasing the probability of identifying patients affected by the pathology when they are pre-symptomatic, plays an important role in contributing to potential therapeutic outcomes – specifies Marika Pane, clinical director of the Nemo Pediatric Center in Rome and Associate Professor of Child Neuropsychiatry at the Catholic University of Sacred Heart of Rome –. It is therefore necessary to take into account the fact thathe degeneration of motor neurons begins before birth, it escalates rapidly and that the process cannot be reversed. The innovative aspect of this treatment is that it intervenes directly on the genetic defect with a single administration; Therefore, it is carried out only once in a lifetime. Based on the clinical studies available, early treatment allows young patients to achieve motor development stages that are close to those of healthy peers, such as head control and the ability to sit without supportwithout the need to resort to ventilatory support that the history of the disease normally requires.”

In Italy, treatment has already been administered to 125 children

Onasemnogene abeparvovec it had already obtained approval for reimbursement in Italy in March 2021 as the first single-dose gene therapy for spinal muscular atrophy type 1 (Sma1) designed to directly address the genetic cause of the disease by replacing the function of the missing or non-functioning Smn1 gene to halt disease progression with a single intravenous administration.

Precisely with the advent of gene therapy, the community of SMA patients and their families saw change the natural history of the disease. As demonstrated by the data on the use of onasemnogene abeparvovec in normal clinical practice in Italy (Real World Evidence, RWE), confirming that what is reported by international clinical studies translates into effective benefits for patients treated in our country , Where around 125 children have already been involved.