Biogen’s Salanersen Shows Potential to Address Unmet Needs in Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) remains a serious rare neuromuscular disease characterized by progressive loss of motor neurons. While disease-modifying therapies have changed treatment options for people living with SMA, some individuals continue to experience significant unmet needs despite receiving available therapies.

How could salanersen impact treatment approaches for people living with spinal muscular atrophy?

In an interview with BioPharm International, Stephanie Fradette, head of Biogen’s Rare Neurology Development Unit, discussed the development of salanersen and the preliminary clinical findings that supported the therapy’s recent FDA Breakthrough Therapy designation.

Fradette, who has spent more than a decade contributing to SMA therapeutic development, explained that the FDA designation is intended for therapies targeting serious conditions where preliminary clinical evidence suggests the potential for substantial improvement over available treatments.

“For FDA Breakthrough Therapy designation, what FDA is looking for are drugs intended to treat a serious condition, which of course SMA remains such, and drugs with preliminary clinical evidence that indicate that the drug has the potential to demonstrate substantial improvement over available therapy,” Fradette said.

The preliminary evidence supporting the designation came from an interim analysis of an ongoing phase 1b study evaluating salanersen in individuals with SMA who had previously received intravenous gene therapy but continued to experience suboptimal clinical outcomes, according to Fradette.

The phase 1b study enrolled 24 participants, all of whom had at least one year of follow-up at the time of the interim analysis. The study evaluated two dose levels of salanersen, 40 mg and 80 mg, administered once annually, across two age cohorts. Although the primary objective of the study was to assess safety, researchers also evaluated biomarker and clinical outcomes.

Fradette noted that both dose levels were generally well tolerated, with most adverse events reported as mild to moderate in severity. These findings supported continued evaluation of salanersen in future stages of development.

Beyond safety, Fradette highlighted changes in neurofilament levels, a biomarker associated with neurodegeneration and axonal injury. Approximately 70% of participants entered the study with elevated neurofilament levels, consistent with ongoing disease activity and limited clinical response despite prior gene therapy.

Among participants with elevated neurofilament levels at baseline, salanersen treatment was associated with an approximately 75% reduction in neurofilament levels six months after treatment initiation, suggesting a potential impact on neurodegenerative processes.

“When we look at our biomarker data and our clinical outcome data, that’s what really gets us excited,” Fradette said.

Fradette also discussed functional improvements observed across the study population, while noting that participants represented different age groups, dose levels, and baseline clinical characteristics, making comparisons across the entire group challenging.

She highlighted one case involving a child who was symptomatic at birth, had two copies of the SMN2 gene, and had previously received both nusinersen and gene therapy. At five years of age, the child had not achieved independent sitting ability when entering the salanersen study. Following treatment with the 80 mg dose, the child achieved the ability to sit without support at day 90 and maintained that milestone at the one-year assessment.

According to Fradette, these types of improvements are notable given the participants’ ages, baseline function, and time since receiving gene therapy.

“It’s early days, but really encouraging as to what salanersen can potentially do and bring to the SMA community,” Fradette said.

As development continues, Fradette emphasized the importance of preserving motor neurons as early as possible in individuals with SMA, given the progressive nature of the disease.

“We only get one pool of motor neurons,” she said. “We have to do as much as possible to preserve the motor neuron pool that we’re given as early as possible.”

About the Speaker

Stephanie Fradette, Head of Biogen’s Rare Neurology Development Unit

Stephanie oversees the advancement of therapies for rare neuromuscular diseases. She joined Biogen in 2009 and has held leadership roles across Research and Development, including Safety, Regulatory, and Clinical Development. Fradette has helped advance therapies for spinal muscular atrophy (SMA), SOD1-ALS, and Friedreich ataxia, and is internationally recognized for her expertise in neuromuscular drug development and the application of neurofilament as a biomarker for disease progression and treatment response.