#MDA2022 – ‘Amazing’ Walking Ability Seen in SMA Children on Spinraza
Most children with spinal muscular atrophy (SMA) who were presymptomatic and treated with Spinraza (nusinersen) in the NURTURE clinical trial are hitting major motor milestones within developmentally normal windows, new data show.
“It’s only getting better. It’s spectacular,” Thomas Crawford, MD, from Johns Hopkins Medical Institute, said in a presentation at this year’s Muscular Dystrophy Association (MDA) Annual Meeting.
Crawford’s talk was titled “Nusinersen Effect in Presymptomatic SMA Infants: 4.9 Year Interim of the NURTURE Study.” The research was funded by Biogen, which markets Spinraza.
Spinraza has been approved for SMA in the U.S. since 2016. In SMA, the body is unable to make SMN protein due to mutations in a gene called SMN1. Spinraza works to boost levels of SMN protein by modulating the activity of a related gene, called SMN2.
The open-label Phase 2 NURTURE clinical trial (NCT02386553) is evaluating the safety and effectiveness of Spinraza, given via injection into the spinal canal every four months, in 25 children genetically diagnosed with SMA. All of the children started treatment prior to showing any overt disease symptoms, before the age of 6 weeks.
Among the children in the study, 15 have two copies of the SMN2 gene, and the remaining 10 have three copies of this gene. (More copies of SMN2 are generally tied to less severe SMA.)
At the MDA conference, Crawford shared interim trial data, as of Feb. 15, 2021, with a median follow-up time of 4.9 years.
All of the children in the study are still alive, and none require permanent ventilation. Four of the children, all with two SMN2 copies, had respiratory events in the first year of life that led to them being placed on ventilation. Three of them remain on ventilation at night with a BiPap.
“In the last three or four years, there’s actually been no new respiratory events in this group,” Crawford said.
All but three of the children had reached the maximum possible score on the CHOP INTEND test, which is designed to measure motor function in children with severe motor impairments. Crawford noted that this score was designed to measure decline as babies progressed with the disease.
“We never thought that what we’d actually look at is these kids getting better,” he said.
CHOP INTEND scores tended to increase more quickly in children with three SMN2 copies — at “pretty much a normal rate,” according to Crawford — while in those with two copies of the gene, scores “lagged behind, but they are steadily improving” and making their way to the maximum possible score. Other assessments of motor function generally showed the same trend.
All 25 of the children have achieved the World Health Organization (WHO) motor milestone of sitting without support, and all but one were able to walk with assistance. Two children, currently about 4 and 5 years old, cannot walk on their own.
“Otherwise, everybody is walking alone, which is amazing,” Crawford said.
Most of the children achieved these motor milestones within the 99th percentile age window established by the WHO for healthy children: specifically 84% for sitting without support, 60% for walking with assistance, and 64% for walking independently.
More specifically, nearly all of the babies with three SMN2 copies hit these motor milestones within typical developmental windows. Those with two SMN2 copies were more likely to hit these milestones at a later age than is typical.
“The latest results from the landmark NURTURE study continue to show that most infants who began treatment with Spinraza before the clinical onset of symptoms achieved motor milestones in timeframes consistent with normal development,” Maha Radhakrishnan, MD, Biogen’s chief medical officer, said in a press release.
None of the motor gains seen in the study have been lost over time, and new gains are continually being made as the children grow. No new safety issues have been reported.
“Adverse events were minimal. Essentially, there were no adverse events associated with the drug itself,” Crawford said.
He added that lumbar puncture — the procedure to administer the drug into the spine, usually done under anesthesia — is generally well-tolerated by the children.
“I joke that I’m the chief backstabber,” Crawford said. “I’ve literally done a lot of backstabbing in the last six years, but overall they are very well-tolerated.”
Editor’s note: The SMA News Today team is providing coverage of the 2022 MDA Clinical and Scientific Conference March 13–16.