Biogen (Nasdaq: BIIB) revealed that the US FDA has granted salanersen (BIIB115) Breakthrough Therapy Designation (BTD) for the treatment of spinal muscular atrophy (SMA). The designation is supported by exploratory Phase Ib data showing that children with SMA who had a suboptimal response to prior gene therapy experienced reductions in a neurodegeneration biomarker and gains in motor function following intrathecal salanersen. The designation signals regulatory recognition that as an antisense oligonucleotide (ASO) with a potential once-yearly dosing schedule, salanersen may offer improvement over the current standard of care.
BTD provides intensive FDA guidance throughout development, eligibility for rolling review of the New Drug Application, and typically confers Priority Review upon submission. No prior expedited designations for salanersen have been disclosed publicly.
Salanersen is an intrathecally administered ASO designed to correct splicing of SMN2 pre-mRNA, increasing production of functional survival motor neuron (SMN) protein. The compound incorporates a novel chemistry platform that confers higher potency than earlier-generation ASOs, enabling the once-yearly 80 mg dosing schedule being evaluated in Phase III. Biogen licensed global development, manufacturing, and commercialization rights from Ionis Pharmaceuticals in a 2018 strategic collaboration.
The BTD is grounded in data from a Phase Ib study (n=24, aged 0.5–12 years) in children with SMA who had previously received gene therapy with onasemnogene abeparvovec and had a suboptimal clinical outcome. All participants received at least two intrathecal doses of salanersen at either 40 mg or 80 mg. As per data presented at the 2026 Muscular Dystrophy Association Clinical & Scientific Conference in March 2026, in participants with elevated baseline neurofilament light chain (NfL) concentrations — a circulating marker of ongoing neurodegeneration — salanersen produced a 75% reduction in NfL levels at six months, with reductions sustained throughout the follow-up period. All 24 participants also showed an increase from baseline on at least one motor endpoint.
The Phase III program comprises three global studies. STELLAR-1 (recruiting) is an open-label study evaluating salanersen in treatment-naïve, presymptomatic infants under six weeks of age with a genetic diagnosis of SMA. SOLAR (recruiting) is an open-label study in teenagers and adults aged 15–60 years who are either treatment-naïve or previously treated with risdiplam. STELLAR-2, a randomized, double-blind, sham-controlled study evaluating salanersen initiated approximately six months after onasemnogene abeparvovec in presymptomatically treated infants, was expected to begin recruitment in June 2026. All three studies are evaluating the 80 mg once-yearly intrathecal dose.
Research context
SMA is caused by loss-of-function mutations in SMN1, affecting approximately 1 in 10,000 live births and representing a leading cause of genetic infant mortality. Three mechanistically distinct approved therapies exist: nusinersen (Spinraza, Biogen/Ionis), an intrathecally administered ASO approved by the FDA in December 2016 that also targets SMN2 splicing but requires maintenance dosing every four months; risdiplam (Evrysdi, Roche), an orally administered small-molecule SMN2 splicing modifier; and onasemnogene abeparvovec (Zolgensma, Novartis), an intravenous adeno-associated virus gene therapy approved for patients under two years of age. Despite this landscape, a subset of patients — particularly those who received gene therapy early but achieved suboptimal motor outcomes — have no approved rescue or follow-on option. The Phase Ib population studied for salanersen directly targets this gap.
Salanersen’s mechanistic overlap with nusinersen is direct: both are intrathecally administered SMN2 splice-switching ASOs. The differentiation lies in chemistry. Salanersen’s novel backbone chemistry delivers higher potency, enabling once-yearly dosing compared with nusinersen’s four-monthly maintenance schedule — a distinction with practical implications for patient and caregiver burden. Whether the potency advantage translates to superior efficacy in a controlled comparison remains to be established in Phase III.
This article was generated with AI assistance and reviewed and edited by the AllSci editorial team
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