Newborns given Spinraza still show motor, health gains 5 years later
NURTURE clinical trial supporting newborn screening, early start on treatment
Children diagnosed with spinal muscular atrophy (SMA) and started on Spinraza (nusinersen) as presymptomatic newborns safely continue to achieve motor milestones with no need for permanent ventilation after five years of treatment, updated data from the ongoing NURTURE trial show.
For the majority of trial children with two copies of the SMN2 gene, expected to have more severe disease, better responses to the therapy tended to be in those with more preserved motor nerve cells and intact reflexes at the study’s start. One was able to walk without assistance.
“These results demonstrate long-term treatment effect across approximately 5 [years] and emphasize the value of early diagnosis, inclusion of SMA in recommended national uniform newborn screening panels, and early [Spinraza] initiation in the presymptomatic stage,” the researchers wrote.
Full five-year trial findings, discussed in part at a 2022 scientific conference, are in the study “Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study,” published in the journal Muscle and Nerve.
Children in NURTURE clinical trial started treatment before 6 weeks of age
Biogen’s Spinraza works to boost production of the SMN protein that’s lacking for SMA patients, a disease caused by mutations in the SMN1 gene. It does so by increasing the activity of SMN2, a gene that also has SMN-producing capabilities.
The open-label Phase 2 NURTURE study (NCT02386553), which runs through January 2025, is evaluating Spinraza’s safety and efficacy in 25 children genetically diagnosed with SMA as newborns and without overt symptoms.
All started treatment with Spinraza prior to six weeks of age, given via injection into the spinal canal every four months.
Among them, 15 had two copies of the SMN2 gene, and the remaining 10 had three copies. Based on this, they would be expected to develop SMA types 1 or 2. The number of copies a person has of SMN2 is thought to influence SMA severity, with more copies generally linked to a milder disease course.
As of the last published trial analysis, covering a median three years of treatment with a cutoff date of January 2019, all 25 NURTURE participants were alive, able to breathe on their own, and reaching and maintaining developmentally appropriate motor milestones.
That is a notable contrast to the disease’s natural progression, where children with SMA types 1 and 2 generally never achieve the ability to walk. Type 1 children also require permanent ventilation and typically die shortly after their first year of life, the researchers noted.
All 25 children able to sit without support, many reach normal motor milestones
New interim data with five years of Spinraza’s use and a cutoff date of February 2021, show all 25 children — with a median age of 4.9 — alive and continuing in the study.
“Two additional years of follow-up in NURTURE … demonstrate durability of benefit with continued improvement,” the researchers wrote.
All were able to sit without support, and the likely type 1 child who advanced from crawling to walking with assistance and then to walking independently did so since the 2019 published analysis.
The 10 children with three SMN2 copies achieved expected motor milestones — sitting without support, standing with assistance, crawling, walking with assistance, and standing alone and walking alone — in normal time frames, although one child was slow in being able to walk with assistance.
Among the 15 children with two SMN2 copies, all were able to sit without support. Most, 14, could walk with assistance, and 13 could stand and walk alone. Some in this group achieved these milestones in normal developmental time frames.
Motor function also continued to improve, with steady gains seen in average scores on the Children’s Hospital of Pennsylvania – Infant Test of Neuromuscular Disorders (CHOP-INTEND) and Hammersmith Functional Motor Scale Expanded (HFMSE) over time.
They all continued to grow and gain weight. Compound muscle action potential (CMAP) amplitudes — an indicator of motor nerve health — tended to increase over the first year of treatment, indicating a rise in the number of intact and available motor nerve cells, before stabilizing. CMAP amplitudes were generally lower in children with two SMN2 copies.
Better therapy responses in likely type 1 SMA children with healthier reflexes
Eight children — all with two SMN2 copies — required respiratory support, a feeding tube, or evidenced SMA symptoms by age 2. Their characteristics included low CMAP amplitudes, a loss of muscle reflexes (areflexia), and/or elevated blood levels of neurofilament heavy chain, a marker of nerve damage.
Children with two SMN2 copies with higher CMAP amplitudes and without areflexia at the study’s start tended to have better responses to treatment, with none requiring respiratory or feeding support.
No new safety concerns after five years of Spinraza were noted.
Researchers noted that the gains made in patients starting treatment before symptom onset favorably compare with symptomatic SMA children who started treatment at later ages in other Spinraza clinical trials.
“NURTURE thus demonstrates the pathway of more normal developmental maturation is restored by [Spinraza]-induced amelioration of SMA-associated degeneration: the earlier this begins, the better the outcome,” the researchers wrote.
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