Good news for the community of SMA patients and their families comes from the approval by the Italian Medicines Agency Aifa to the extension of the first gene therapy for SMA to type 2 SMAonasemnogene abeparvovec (Zolgensma®), approved in 2021 for Sma 1. Now, the extension of the approval also allows it to be administered to children with Sma 2 up to 13.5kg and to pre-symptomatic people with 3 copies of the Smn2 gene.
Spinal muscular atrophy (Sma) is a rare and serious neuromuscular disease, as well as the leading cause of genetic childhood death, characterized by progressive loss of muscle function, compromising movement, breathing and swallowing, which occurs when the version of a gene needed to produce an essential protein known as “survival motor neuron” (SMS) protein is missing or defective. Own with the advent of gene therapy, the community of SMA patients and their families has seen the natural history of the disease change. Gene therapy is effective in allowing neuromotor development completely comparable to that of children without a diagnosis. But only if it is taken promptly and before the appearance of irreversible symptoms.
“This is another incredible step forward for our community,” he commented Anita Pallara, president of Famiglie Sma. «Faced with the therapeutic revolutions we are experiencing, we are able to perceive the effectiveness of our efforts, those of the scientific community and companies. At the same time, thanks to these epochal changes, patients’ expectations and needs are changing. This is a chapter yet to be written, but in the meantime SMA still exists: early diagnosis is therefore fundamental because at the moment we have the possibility of radically changing people’s lives but we need to arrive in time. The lack of widespread newborn screening throughout Italy creates class A and class B children depending on the region of birth. This is unacceptable. Let’s think about the tragedy of those who know of the existence of the drug but arrive at the diagnosis when it is too late. The entire system that revolves around SMA must mobilize for this.”
The pharmacological revolution was a radical change for clinicians too, as he confirms Marika Pane, clinical director of the Nemo Pediatric Center in Rome and associate professor of child neuropsychiatry at the Catholic University of the Sacred Heart of Rome, which recalls «a twenty-year journey. We had nothing to offer except a deadly diagnosis for every young couple who arrived with a little bundle with signs of illness. After the unfortunate news, we needed some time to reflect. Today, however, the news of a diagnosis remains we show them the development curves of young patients with SMA which are completely comparable to those of children without a diagnosis, because they maintain the developmental stages of their peers.”
SMA type 1, whose symptoms develop at the age of 6 months and will lead to death or permanent ventilation within two years, and SMA type 2, with symptoms that appear between 6 and 18 months of age and the child he will never walk but could suffer from worsening scoliosis and respiratory failure. «We must take into account the fact that the degeneration of motor neurons begins before birth, intensifies rapidly and that the process cannot be reversed» explains Pane. «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. Via viral vector, the therapy acts as a band-aid on the diseased genewhich produces protein that is missing, thus blocking the arrival and evolution of symptoms. The limit in the eligibility criteria for therapy is the child’s weight of 13.5 kg. But the American FDA and European EMA agencies have already extended it to 21 kg, we are awaiting the results of a safety and efficacy study also on heavier patients.”
In our country, between clinical studies and clinical practice, they have already been involved approximately 125 children with SMA 1 and it is expected to treat another 5-6 with form 2; there are 16 centers that have treated at least one child. However, “it is important that the centers meet certain characteristics; patients must be closely monitored, blood parameters, closely monitored to identify serious or very serious side effects”.
“The patients treated in the world are 3700 so far between expanded access, clinical studies and use in clinical practice, which together with the prolonged period of observation of the stages has allowed us to consolidate the results of efficacy and safety” Roberta Rondena, Country Value & Access Head di Novartis. The treatment involves a single intravenous administration, «For those who cannot tolerate it for safety reasons, two international studies on intrathecal administration are underway. Novartis’ commitment to this therapeutic area will continue to reach more and more patients and ensure that all eligible people can have access to treatment.”
The challenges for Sma Families are never over. Tells Anita Pallara that «on March 28, a 10-month-old Palestinian baby arrived in Italy, accompanied by his mother and father, the other little brothers who remained in Palestine. They had contacted me directly and, thanks to the Puglia Region which welcomed them, and to the efforts of Novartis, we managed to ensure that the little one, with severe SMA, completely hypotonic, received the treatment about ten days ago. I visit them often and one afternoon I saw him move in the cot and turn to look at me. We always talk about screening and new therapies, but I had never seen the effectiveness of gene therapy materialize before my eyes. They will remain here for three months to carry out the necessary checks. Being born in the right part of the world is a great fortune. Our challenge now is to help all children and bring our privilege beyond our borders.”
Photo: presentation press conference