MDA 2026: Salanersen improves motor function in SMA kids after gene therapy
Trial analysis shows 'new motor milestones' for children on once-yearly treatment
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Salanersen, a treatment candidate for spinal muscular atrophy (SMA) now in clinical testing, is safe and was shown to stabilize or improve motor function over at least one year of follow-up in children with SMA who had previously been treated with gene therapy but did not respond as well as expected.
That’s according to a new interim analysis of data from a Phase 1b clinical trial (NCT05575011), sponsored by salanersen developer Biogen, which found that use of the experimental therapy led to gains in motor function among children in the study.
These children, most of them older, did not have a good enough response to prior treatment with Zolgensma (onasemnogene abeparvovec-xioi), and some who showed motor function benefits with salanersen had received the gene therapy years prior, the analysis found.
According to Diana Castro, MD, a neurologist at the Rare Disease Center in Denton, Texas, who shared the trial data, clinicians don’t typically expect these youngsters to gain motor function.
“The fact that we’re seeing improvements here [is] quite remarkable,” Castro said in a presentation at the Muscular Dystrophy Association’s 2026 MDA Clinical & Scientific Conference, held this week in Orlando, Florida. The poster was titled Phase 1 Interim Results Evaluating the Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of Salanersen for Spinal Muscular Atrophy.” Several of the report’s authors are employees of Biogen.
In a company press release detailing these “additional results,” Biogen stated that these “salanersen data [show] new motor milestones achieved in children with SMA previously treated with [the] gene therapy [Zolgensma].”
Mutations in the SMN1 gene cause SMA by reducing the amount of working survival motor neuron (SMN) protein. Without enough of the SMN protein, the specialized nerve cells that control movement are progressively lost, leading to characteristic SMA symptoms of muscle wasting and weakness.
Salanersen similar to Spinraza, but requires fewer doses
Salanersen, given as an injection directly into the spinal canal (intrathecal injection), targets the SMN2 gene. Like SMN1, that gene contains a genetic template that cells can use to produce SMN.
Because of a small difference in the genetic code, SMN2 typically produces much less working protein than SMN1. Salanersen is a type of molecule called antisense oligonucleotide (ASO) that binds to messenger RNA (mRNA), an intermediary template for protein production, that is transcribed from SMN2. By binding to SMN2 mRNA, salanersen intends to increase the production of full-length, functional SMN protein.
This is similar to how Biogen’s Spinraza (nusinersen), an already approved ASO-based therapy for SMA, works. The company designed salanersen to be more effective than Spinraza and to require less frequent dosing — once a year.
Spinal muscular atrophy has benefitted from extraordinary therapeutic progress, but across the treatment landscape there remains room for improvement. … There is growing scientific and clinical enthusiasm about the advances that salanersen offers.
Spinraza’s approved regimen involves three loading doses every two weeks, and a fourth 30 days later. After that, patients are given maintenance doses once every four months. A higher dose regimen of Spinraza has been approved in the European Union and Japan; a decision in the U.S. is expected in early April.
“Spinal muscular atrophy has benefitted from extraordinary therapeutic progress, but across the treatment landscape there remains room for improvement,” said Thomas Crawford, MD, codirector of the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine in Baltimore.
According to Crawford, “there is growing scientific and clinical enthusiasm about the advances that salanersen offers.”
5-year-old in trial now able to sit without support
The Phase 1b study, launched in 2022, was designed to test the safety of salanersen and to look for early signs of effectiveness. It involves 24 children, ages 6 months to 12 years, who had received Zolgensma at least six months prior. Some of the youngsters had been given Spinraza or Evrysdi (risdiplam), another approved SMA therapy, before receiving Zolgensma.
In the study, participants have been given salanersen as an intrathecal injection each year. For the first two years of the study, the children receive either 40 or 80 mg of therapy. Then, all patients take the higher dose for a long-term extension period.
The preliminary analysis, in which all patients were followed up for a minimum of one year, showed that half of them achieved at least one new World Health Organization motor milestone. These included sitting without support, crawling, standing, or walking.
As an example, Castro highlighted one participant who, prior to receiving salanersen, was never able to sit without assistance.
“The patient was enrolled in the study at 5 years of age, and three months later, after getting the first dose, the patient was able to start sitting without support,” Castro said.
There were also other signs of improved motor function. Children as old as 2 at the study’s start showed improvements in two SMA motor rating systems. On one, the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), all four children treated with 80 mg salanersen were above the minimum threshold for clinically meaningful improvement a year later.
And, at about 1.5 years, the same was seen for the three children taking the lower dose, according to Castro.
Castro noted that improvements seen using the other scale, the Hammersmith Infant Neurological Examination Section 2, tended to be faster and more pronounced in the 80 mg treatment group.
Again, using two motor function scales, most children older than 2 also experienced benefits after one year, Castro said.
Biogen is advancing 3 Phase 3 trials to test therapy
Biomarker data further showed that elevated levels of neurofilament light chain (NfL), a marker of ongoing neurodegeneration, were reduced by 75% at six months. Moreover, these levels stayed low throughout the follow-up period, per Castro.
Participants generally tolerated the treatment well, and “the safety was very similar to what we … have experienced with [Spinraza] over the years,” Castro said.
Most side effects were mild or moderate. No serious safety events were considered related to salanersen in the interim analysis.
Based on these Phase 1b findings, Biogen is advancing three Phase 3 trials to test salanersen at the 80 mg dose. The first, STELLAR-1 clinical trial (NCT07221669, is already recruiting presymptomatic newborns with SMA. STELLAR-2 (NCT07444450), which will involve infants previously given Zolgensma, is not yet recruiting. Enrollment has also not yet started in SOLAR (NCT07444476), which will involve older teenagers and adults.
“With the encouraging Phase 1b results in hand, we are initiating the Phase 3 STELLAR-1, STELLAR-2, and SOLAR salanersen studies as quickly as possible,” said Stephanie Fradette, head of the neuromuscular development unit at Biogen. “Together with the SMA community, we have designed these studies to confidently answer the most relevant questions for the field and establish salanersen’s role in the future treatment landscape.”
According to Biogen, salanersen has “the potential to deliver high efficacy in SMA.”
Note: The SMA News Today team is providing live coverage of the 2026 MDA Clinical & Scientific Conference March 8-11 in Orlando, Florida. Go here to see the latest stories from the conference.
