Breathing difficulties in SMA eased with Zolgensma in real-world study
Treatment with the approved gene therapy Zolgensma was found to ease breathing difficulties in children with spinal muscle atrophy (SMA), reducing hospitalizations due to respiratory issues by than 25%, according to a real-world study in Israel.
Daily ventilation time — the period when some children used mechanical devices to aid breathing — also decreased, from more than 14 hours per day to about 11 hours, one year into Zolgensma therapy.
“Our real-world analysis suggests [Zolgensma] may improve respiratory outcomes,” the researchers wrote, noting that their findings add to the limited data on the gene therapy’s impact on breathing difficulties outside clinical trials.
The team noted, however, that “age at treatment and treatment combinations may also influence [the] respiratory trajectory” of children with SMA.
Their study, “Respiratory outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy: national real-world cohort study,” was published in the European Journal of Pediatrics.
Daily ventilation time for Zolgensma-treated children dropped by 3 hours
SMA is caused primarily by mutations in the SMN1 gene, which contains the genetic code for the protein SMN. These mutations lead to the progressive loss of motor neurons, the specialized nerve cells that control voluntary movement in the body, leading to muscle weakness and wasting.
Severe weakness in the muscle walls supporting the chest wall is common in patients with SMA types 0, 1, or 2, which occur before birth (type 0) or typically manifest in infancy. Such weakness causes breathing complications, including shallow breathing, lung underdevelopment, and lung infections. Patients with severe breathing difficulties may need ventilation support to assist them in breathing.
Zolgensma, the first approved gene therapy for SMA, is now available in more than 50 countries worldwide. It contains a harmless virus that delivers a working copy of SMN1 to the body’s cells. With this working gene, motor neurons and other cells can produce functional SMN protein.
This therapy has been shown to improve and maintain motor function in clinical trials, but real-world data are needed to better understand how Zolgensma treatment affects SMA patients’ breathing difficulties and other symptoms, according to the researchers.
To that end, a team of researchers from several institutions in Israel studied 25 children with SMA who received Zolgensma at a median age of 6.1 months. Among them, 23 had SMA type 1 and 2 had SMA type 2; the median age at diagnosis was 3 months.
Some of the patients had received other approved treatments prior to Zolgensma: Eight were given Spinraza (nusinersen) and one had received Evrysdi (risdiplam).
At the beginning of the study, six children (24%) required noninvasive ventilation for an average of 14.3 hours per day.
By the end of the study, one year after treatment with Zolgensma, 10 children (43%) were using noninvasive ventilation. However, the average daily ventilation use decreased to 11.1 hours per day.
All those who used noninvasive ventilation one year after Zolgensma treatment had received the gene therapy, or Spinraza or Evrysdi, before 6 months of age. Those children who had prior treatment with Spinraza or Evrysdi and required noninvasive ventilation were treated with Zolgensma when they were between 1 year and almost 2 years old.
Zolgensma plus other therapies may best ease breathing difficulties
The researchers found a 26% decrease in the frequency of respiratory-related hospitalizations during the follow-up period, with inpatient stays reduced from 0.76 to 0.57 per year.
That percentage was much higher among the 12 children who had SMA type 1, were alive one year post-Zolgensma treatment, and did not receive Spinraza or Evrysdi previously. For this subset of patients, respiratory-related hospitalizations were reduced by 64%, from 2.1 to 0.75 per year.
“This reduction in hospitalizations is significant for patients and their families by helping to maintain the patient’s quality of life at home, which is pivotal to their overall physical and mental well-being,” the researchers wrote. “Moreover, reducing hospitalization days is cost-effective for both the healthcare system and the patient’s caregivers.”
This reduction in hospitalizations is significant for patients and their families by helping to maintain the patient’s quality of life at home, which is pivotal to their overall physical and mental well-being.
The researchers also looked at how the children were fed one year after Zolgensma treatment, noting that they believed this was a critical component of respiratory health.
“Feeding and swallowing abilities are crucial for maintaining respiratory health in SMA patients,” the team wrote.
At the study’s start, 20 of the 25 patients maintained full oral nutrition. After one year, 15 of the surviving 23 patients were fed orally, with four other patients requiring feeding through a gastrostomy tube, for a total of eight.
Among the 12 patients who had been treatment-naive, six could be maintained on oral feeding one year into Zolgensma therapy.
The researchers suggested that combining Zolgensma treatment with other therapies, such as Spinraza or Evrysdi, could be beneficial.
“The differences between treatment-naive patients and those previously treated with [Spinraza or Evrysdi], observed by us and others, suggest possible synergy between treatments and combined positive effects on respiratory outcomes,” the researchers wrote, adding that these “real-world findings emphasize the need for comprehensive, standardized, long-term respiratory management of SMA.”
Among the study’s limitations, the scientists noted that a follow-up period of one year may not be enough to adequately assess the impact of Zolgensma treatment.
The post Breathing difficulties in SMA eased with Zolgensma in real-world study appeared first on SMA News Today.
