sma | MY SPECIAL DOCTOR

Approved in Italy Nusinersen for the treatment of patients with SMA, a rare genetic neuromuscular disease that predominantly affects children and is the leading genetic cause of infant mortality. Data from clinical trials have shown significant results in terms of increased survival in children with the disease and achievement of important developmental motor milestones, such as head control, sitting, crawling and walking. Italy an example of excellence in the world for accelerated time to approval and access to the new therapy.

What is SMA
Spinal muscular atrophy (SMA) is characterized by the loss of motor neurons in the spinal cord and brainstem, resulting in severe and progressive muscle weakness and atrophy. Individuals with the most severe Type of SMA may eventually go into paralysis and have difficulty maintaining vital functions, such as breathing and swallowing.

Due to the loss or defect in the SMN1 gene, people with SMA do not produce sufficient amounts of SMN protein, which is critical for motor neuron survival. The severity of SMA correlates with the amount of SMN protein. Individuals with Type 1 SMA, the most severe form, produce very low amounts of SMN protein and do not achieve the ability to sit without aids or live beyond two years without respiratory support. Individuals with Type 2 and Type 3 SMA produce a higher amount of SMN protein and have less severe forms of SMA, but still capable of changing life expectancy and quality of life.

Approval
Nusinersen constitutes the first treatment for this disease approved in Italy; the drug was reviewed under the Italian Medicines Agency’s accelerated approval pathway, aimed at speeding up access to drugs that treat serious or life-threatening diseases and generally address unmet clinical needs.

The approval of nusinersen is largely based on the results of two multicenter, controlled registrational studies, including the final data from the ENDEAR study (for childhood-onset SMA) and the interim data from the CHERISH study (for late-onset SMA), which demonstrated clinically and statistically significant efficacy and favorable benefit-risk profile of nusinersen. The approval was further supported by data from the open-label NURTURE study, obtained in pre-symptomatic individuals genetically diagnosed with SMA and with the possibility of developing SMA Type 1, 2, or 3.

Nusinersen is administered intrathecally, that is, via a lumbar puncture directly into the cerebrospinal fluid (CSF) around the spinal cord, the site of motor neuron degeneration caused by insufficient levels of SMN protein in SMA patients.

Spinalmuscular atrophy (SMA) is one of those rare diseases, moreover chronic, for which treatment is finally looming from a clinical perspective. It affects about 1 in 10,000 infants, is characterized by progressive motor neuron death, resulting in disabling muscle weakness, and is the most common genetic cause of infant death.

“We were used to dealing with a condition that was progressive and whose only treatments were palliative, now we have good therapeutic responses, although they differ depending on clinical severity and the timing at which treatment is administered from the onset of symptoms.” says Enrico Bertini, Director of the Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, Department of Neuroscience, Bambino Gesù Children’s Hospital, Rome.

A white paper has recently been published on the topic.
“Sma. A Tale of a Revolution”
, produced by Biogen with author Claudio Barnini (downloadable from the link)and in collaboration with the Sma Families Association, which explains how standards of care have changed in just a few years.

“Ten years ago, the first guidelines were published, which provided important recommendations on the clinical care of patients,” notesProf. Eugenio Mercuri, director of the Child Neuropsychiatry Operating Unit at Policlinico Gemelli in Rome. These early guidelines led the way and introduced for the first time the importance of having careful monitoring of certain aspects of the disease, leading to increased survival and the reduction and prevention of many complications. Since then, new needs have emerged that have led to a lengthy review, culminating in 2017 with the publication of recommendations that focus on the day-to-day aspects of disease management. One of the innovations is an attempt to improve and implement more prevention by providing guidance to family and area physicians.”