SMA gene therapy Zolgensma helps kids after tracheostomy
Study finds no new safety risks for children who have had procedure
- Zolgensma improved motor function in SMA children with tracheostomies.
- No new safety risks were observed for SMA patients with tracheostomy who received Zolgensma.
- Many patients received Spinraza or Evrysdi alongside Zolgensma.
Treatment with Zolgensma (onasemnogene abeparvovec-xioi) improved motor function in children with spinal muscular atrophy (SMA) who needed tracheostomy, without posing new safety risks, a real-world study showed.
Tracheostomy is a surgical procedure that creates an opening in the windpipe, often necessary when a ventilator is used to assist with breathing.
“These real-world data support [Zolgensma] treatment for patients with SMA and tracheostomies and can inform future access, treatment, and care decisions,” the researchers wrote.
The study, “Trach and treat: Safety and motor outcomes following onasemnogene abeparvovec in patients with spinal muscular atrophy and tracheostomies in the RESTORE registry,” was published in the Journal of Neuromuscular Diseases.
SMA is caused mainly by mutations in the SMN1 gene that result in an inadequate amount of SMN, a key protein for the survival of motor neurons, which are the nerve cells that control movement. This causes the progressive loss of motor neurons and SMA symptoms such as muscle weakness and wasting. Breathing issues in SMA may require respiratory support, which in some cases may include tracheostomy to allow direct airway access and effective airway clearance.
Motor function improves
An international team that included scientists from Novartis, which markets Zolgensma, evaluated the gene therapy’s safety and efficacy in children who underwent tracheostomy. They analyzed data from 34 children enrolled in the RESTORE international registry (NCT04174157), 14 of whom underwent tracheostomy before Zolgensma and 20 after.
All participants had symptoms when they were diagnosed with SMA, which occurred at a mean age of 4 months. Most patients (76.5%) were also treated with Spinraza (nusinersen) or Evrysdi (risdiplam) before or after Zolgensma. The gene therapy was administered at a mean age of 9.5 months.
Motor function and motor milestones were assessed with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), the Hammersmith Functional Motor Scale – Expanded, and the Hammersmith Infant Neurological Examination – Section 2.
Seven of eight children who underwent tracheostomy before Zolgensma whose motor function was assessed at least twice at different points in time maintained or achieved motor milestones and/or had stable or improved motor function on at least one scale after receiving the gene therapy.
These milestones included head control without support, sitting alone for 30 seconds or longer, rolling from both sides, or supporting their own weight for at least 2 seconds.
All 11 children whose tracheostomies were performed after Zolgensma and with two or more motor assessments in a specific test maintained or achieved motor milestones, including head control and rolling from both sides, and/or had stable or improved motor function on at least one scale.
Most patients experienced treatment-emergent adverse events (TEAEs), which are unexpected complications that occur during the course of treatment. In about two-thirds of patients, these events were severe. Four TEAEs were deemed Zolgensma-related.
Frequently reported adverse events included transient decreases in platelet levels (35.3%), heart issues (29.4%), and liver toxicity (23.5%). Four children died, three due to respiratory failure not related to Zolgensma and one of unknown cause.
“Compared with patients without tracheostomies, no increased incidence of TEAEs was observed for those who received [Zolgensma] before or after tracheostomy, or for those who received combination versus monotherapy,” the researchers wrote.
The data “indicate that patients with tracheostomies who were treated with [Zolgensma] demonstrated no increased safety risks compared with other children with SMA and, overall, exhibited positive motor outcomes regardless of whether they received other treatments before or after [Zolgensma],” they wrote.
“These findings suggest a positive benefit-risk profile for treatment in this population,” the team concluded.
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