Biogen Inc. announced topline results from its Phase 1 study of salanersen (BIIB115/ION306), an investigational antisense oligonucleotide for spinal muscular atrophy (SMA) that demonstrated substantial slowing of neurodegeneration and clinically meaningful improvements in motor function. The company is now engaging with global health authorities to advance the drug directly to Phase 3 registrational studies.
Novel Antisense Approach Shows Promise
Salanersen leverages the same mechanism of action as Biogen's approved SMA treatment SPINRAZA (nusinersen) but is designed to achieve greater potency and enable once-yearly dosing. The Phase 1 study evaluated the drug in pediatric participants with SMA who had previously received ZOLGENSMA (onasemnogene abeparvovec) gene therapy and had investigator-reported suboptimal clinical status.
In the interim analysis of 24 participants who received either 40 mg or 80 mg salanersen once yearly, both dose levels were generally well-tolerated and led to substantial reductions in neurofilament light chain (NfL), a biomarker of ongoing neurodegeneration. Participants with elevated baseline NfL concentrations experienced mean reductions of 70% at six months, which were sustained through the one-year dosing interval.
Unexpected Motor Function Gains
The most striking results came from exploratory clinical outcome data in a subgroup of eight participants aged 2-12 who received 40 mg of salanersen and had at least one year of follow-up. Half of these participants achieved new World Health Organization motor milestones they previously could not accomplish independently, including walking, crawling, standing, or sitting without support.
"To see a child dosed with gene therapy at one year of age and still unable to sit without support at age five then gain the ability to sit independently just 3 months after initiating salanersen, that is unexpected," said Valeria A. Sansone, M.D., Ph.D., Clinical and Scientific Director at the Clinical Center NeMO in Milan and principal investigator for the study.
The participants also demonstrated clinically meaningful improvements in standardized motor function assessments, with a 3.3-point mean improvement on the Hammersmith Functional Motor Scale – Expanded (HFMSE) and a 5.3-point improvement on the Revised Upper Limb Module (RULM) from baseline to one year.
Safety Profile and Development Timeline
The cumulative Phase 1 data indicate salanersen has a generally well-tolerated safety profile at both tested doses, with most adverse events mild to moderate in severity. The most common adverse events were pyrexia and upper respiratory tract infection.
"Despite the remarkable therapeutic advancements in the field of SMA over the past decade, there remains critical unmet needs. Salanersen represents the next phase of Biogen's ongoing pursuit to address these needs," said Stephanie Fradette, Pharm.D., Head of the Neuromuscular Development Unit at Biogen.
The Phase 1 study consisted of two parts: a randomized, placebo-controlled segment in healthy adult male volunteers and an open-label segment in pediatric SMA participants. Biogen licensed the global development, manufacturing and commercialization rights for salanersen from Ionis Pharmaceuticals, which discovered the drug.
Addressing Unmet Medical Needs
SMA is a rare genetic neuromuscular disease affecting approximately 1 in 10,000 live births and is characterized by progressive muscle atrophy and weakness due to motor neuron loss. The disease is caused by deficiency in survival motor neuron (SMN) protein production due to a damaged or missing SMN1 gene.
Current treatment options include Biogen's SPINRAZA, which requires intrathecal administration every four months after initial loading doses, and gene therapies like Novartis' ZOLGENSMA. More than 14,000 individuals worldwide have been treated with SPINRAZA, which has demonstrated efficacy across ages and SMA types with data in patients treated up to 10 years.
The potential for once-yearly dosing with salanersen could represent a significant advancement in SMA care, particularly for patients who have suboptimal responses to current therapies. Biogen plans to study salanersen in both previously treated and treatment-naïve patients in the upcoming Phase 3 program.
