#MDA2022 – Data: Zolgensma Given After 6 Months Benefits SMA Babies
Even when given to young children with spinal muscular atrophy (SMA) at ages older than 6 months, the gene therapy Zolgensma (onasemnogene abeparvovec) can improve motor function, an analysis of real-world data show.
Indeed, more than 70% of babies treated between 6 and 24 months had better scores on a standardized test of motor function after receiving Zolgensma — with scores indicating improvements over time — according to researchers.
These data “continue to reinforce the consistent, significant and clinically meaningful therapeutic benefit of Zolgensma in the real-world setting, including in patients outside of our current clinical trial experience,” Shephard Mpofu, MD, chief medical officer at Novartis Gene Therapies, which manufactures Zolgensma, said in a press release.
The findings were presented at the Muscular Dystrophy Association (MDA) 2022 Annual Meeting, in a poster titled “Effectiveness and safety of onasemnogene abeparvovec in older patients with spinal muscular atrophy: real-world outcomes from the RESTORE registry.” The study was funded by Novartis.
Zolgensma is a one-time gene therapy that works to deliver a healthy copy of the SMN1 gene to the body’s cells. It is widely available to treat SMA, which is caused by mutations in SMN1.
Like other SMA treatments, Zolgensma is thought to be helpful for preventing SMA symptoms from worsening, but generally does not repair damage that has already occurred. As such, outcomes generally are better when treatment is started early in life — generally within a few weeks or months of birth. The impact of treatment when given later in life remains incompletely understood.
Now, researchers at Novartis and other institutions conducted an analysis using data from the RESTORE registry (NCT04174157), a multinational, observational study that is tracking outcomes for patients with SMA for up to 15 years.
“Interventional trials of [Zolgensma] demonstrated safety and efficacy in patients [younger than] 6 months of age,” the researchers wrote. “We aimed to describe real-world outcomes in patients with spinal muscular atrophy (SMA) aged [older than] 6 months at the time of [Zolgensma] infusion.”
As of the data cutoff of Nov. 23, 2021, the researchers identified 145 children with SMA who were given the therapy after the age of six months. Among them, 67 were treated between the ages of 6 and 12 months, 67 between ages 12 and 24 months, and 11 after age 2. Most of the children weighed from 8.5 to 13.5 kg (about 19 to 30 lbs) when they were treated.
Most patients treated from 6 to 12 months had two copies of SMN2 (74.6%), while those treated from ages 12 to 24 months had two (52.2%) or three (47.8%) copies of SMN2. This gene works as a “backup” for SMN1, with more copies generally tied to less severe SMA.
Zolgensma was the only SMA therapy received by 32.4% of the babies, and another 47.6% switched to Zolgensma from Spinraza (nusinersen). The rest were given Zolgensma in combination with Spinraza or other SMA treatments.
Of the babies, 46 had at least two recorded scores on the CHOP INTEND, which is a standardized test used to assess motor function in infants with severe neuromuscular disease.
Most of these babies (71.7%) experienced an increase in CHOP INTEND score of at least four points from their first to their most recent hospital visit, suggesting that their motor function was improving over time. The proportion with such an increase was somewhat higher for younger patients — those treated from ages 6 to 12 months — compared with those treated at 12 to 24 months (82.6% vs. 60.9%).
“Patients with SMA aged [more than] 6 months at [Zolgensma] infusion benefited from treatment as measured by CHOP INTEND scores,” the researchers concluded.
The team added that the safety profile of Zolgensma in these children “is consistent with the overall [safety] profile for [Zolgensma], with no apparent pattern of [side effect] incidence or severity according to age at infusion.”
Editor’s note: The SMA News Today team is providing coverage of the 2022 MDA Clinical and Scientific Conference March 13–16.