2023-07-11 16:03:52
Children who are started on nusinersen before the onset of clinical symptoms of Spinal Muscular Atrophy (Sma) – a rare genetic disease – continue to maintain and achieve new motor development milestones over a five-year period. After an additional two years of follow-up, all patients are still alive, with no need for permanent ventilation, and 23 of 25 children have achieved the ability to walk independently, most within the timeframe expected for their age group. These are the results of the Nurture study published in the journal ‘Muscle & Nerve’ which also provide, in the context of an increasingly widespread newborn screening process globally, further indications on the importance of objective measurement of disease activity in order to define therapeutic expectations based on the baseline characteristics of individual patients.
Sma is a rare disease characterized by degeneration of the anterior horn motor neurons of the spinal cord. Nusinersen – explains the pharmaceutical company Biogen in a note released today – is an antisense oligonucleotide (antisense oligonucleotide or Aso) which acts on the main cause of Sma by continuously increasing the amount of Smn (survival motor neuron) protein produced in the body, deficient in those with the illness. The drug is delivered directly into the central nervous system, where the motor neurons reside, to provide treatment where the disease originates. Approved in more than 60 countries to treat infants, children and adults with SMA, it has been administered to more than 14,000 people worldwide. “In the Nurture study – says Matteo Papi, medical director of Biogen Italia – most of the children treated in the presymptomatic phase have reached the stage of independent walking; many of these achieved this within the typical time window for children of the same age. The data from this important study – he continues – show the effects of early and continuous treatment with nusinersen in the long term and underline the importance of uniformly implementing newborn screening for Sma nationwide, in order to obtain a diagnosis as early as possible. as early as possible”.
The five-year results of the Nurture study – explains the pharmaceutical company – demonstrate that children with three copies of the Smn2 gene (10) managed to reach all the motor development milestones defined by the World Health Organization (WHO) within the set time frame , with the exception of one child who, however, managed to reach the stage of independent walking, on schedule. Among children with two copies of the Smn2 gene (15), all achieved the ability to sit without support and stand with assistance, 14 were able to walk with assistance, and 13 were able to stand and to walk independently; some have reached these developmental milestones in age-appropriate time windows. Since the previous publication of Nurture’s results, two additional children with two copies of the Smn2 gene have achieved the maximum score on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (Chop Intend) at ages 3.8 and 4.8 years bringing the total to 22 children participating in the study (12, or 80%, with two copies of Smn2; 10, or 100%, with three copies of Smn2). No other infants required respiratory intervention as defined by the primary endpoint from the previous data cut-off, when four did require one.
“The scientific community is beginning to recognize the importance of early markers of neurodegeneration in apparently asymptomatic infants with Sma,” comments Thomas Crawford, MD, co-director of the Muscular Dystrophy Association Clinic and professor of neurology at Johns Hopkins University. are evaluated for the first time. Data from the Nurture study show how small differences in baseline characteristics can have a major impact on outcomes, including motor function, lung function, swallowing and feeding. The amplitude of the Cmap and areflexia (which measure muscle activity, Ed) are indicators of the progress of the disease even before the appearance of signs or symptoms; these characteristics – he observes – and others still to be defined, are important for the correct interpretation of the data of the studies that evaluate the therapies for Sma “.
A post-hoc analysis of Nurture data evaluated early markers of disease activity, such as compound muscle action potential (Cmap) and baseline areflexia, under the hypothesis that measures of neuronal damage may indicate disease progression even before the onset of clinical signs and symptoms. Among the results observed was the increase in the percentage of achievement of motor milestones within normal development times and the absence or reduction in the number of children who required respiratory intervention, the positioning of a gastrostomy tube and with presentation of symptoms of Sma within 24 months. The safety profile of nusinersen during this extended follow-up period was consistent with previously obtained data. In the study, 12 participants (48%) developed one or more serious adverse events, none of which were thought to be treatment-related. When analyzed at approximately yearly intervals, the incidence of serious adverse events decreased over time.
Nurtude is an ongoing, open-label Phase 2 study of 25 presymptomatic patients with a genetic diagnosis of Sma (considered to be most at risk of developing Type 1 or 2 Sma) who received their first dose of Nurtude. nusinersen before reaching 6 weeks of age and intends to evaluate the long-term efficacy and safety of the treatment, up to the age of 8 years, to better understand the impact of early treatment.
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