FDA Grants Breakthrough Therapy Designation to Biogen’s Salanersen for SMA

Biogen has received U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation for salanersen (BIIB115), its investigational antisense oligonucleotide for spinal muscular atrophy (SMA). The designation provides enhanced FDA interaction and expedited development pathways for therapies that may offer substantial improvement over available treatments for serious diseases.

The decision was supported by exploratory Phase 1b findings showing clinically meaningful motor improvements and reduced neurodegeneration in children with SMA who had previously received gene therapy but continued to experience suboptimal clinical outcomes.

Scientific Rationale

SMA is a rare genetic neuromuscular disorder caused by insufficient survival motor neuron (SMN) protein, resulting in progressive muscle weakness and loss of motor function. Despite advances in treatment, significant unmet needs remain across the SMA population.

Salanersen is an intrathecally administered antisense oligonucleotide that modifies SMN2 pre-mRNA splicing to increase SMN protein production. Its next-generation chemistry improves potency and supports once-yearly dosing, potentially reducing treatment burden compared with existing chronic therapies. Biogen holds global development and commercialization rights to the therapy under a licensing agreement with Ionis Pharmaceuticals.

Phase 1b Findings

The ongoing Phase 1b study enrolled 24 children aged six months to 12 years who received at least two doses of salanersen at either 40 mg or 80 mg.

Among participants with elevated baseline neurofilament light chain (NfL) levels, a biomarker associated with ongoing neurodegeneration, investigators reported approximately 75% reductions after six months of treatment. These reductions remained sustained throughout follow-up.

Clinical outcomes also showed encouraging activity. All participants improved from baseline on at least one motor assessment endpoint, while 12 achieved at least one new World Health Organization motor milestone. All participants-maintained motor milestones documented at baseline.

Salanersen was generally well tolerated. Most adverse events were mild to moderate in severity. Upper respiratory tract infection and vomiting were most common in the 40 mg cohort, while pyrexia and upper respiratory tract infection were reported most frequently in the 80 mg cohort.

Clinical Implications

Diana Castro, M.D., of the Neurology Rare Disease Center in Texas, said some children previously treated with gene therapy gained critical motor functions, including sitting and walking, after initiating salanersen.

Kenneth Hobby, President of Cure SMA, said the designation highlights persistent unmet needs in SMA and supports accelerated development of promising therapies for the patient community.

Stephanie Fradette, Pharm.D., Head of Biogen’s Rare Neurology Development Unit, said the designation reflects the FDA’s recognition of salanersen’s potential and marks an important milestone for the company’s SMA development program.

Phase 3 Program

Biogen is advancing salanersen through three global Phase 3 studies. STELLAR-1 (NCT07221669) is evaluating presymptomatic infants younger than six weeks, while SOLAR (NCT07444476) is enrolling adolescents and adults aged 15 to 60 years. STELLAR-2 (NCT07444450), expected to begin recruitment in June 2026, will assess salanersen in infants previously treated with onasemnogene abeparvovec gene therapy.

If successful, salanersen could become the first once-yearly SMN-targeting therapy for SMA, potentially expanding treatment options across a broad range of patients.

Reference

Biogen’s Salanersen Receives FDA Breakthrough Therapy Designation for Spinal Muscular Atrophy | Biogen