Biogen’s Salanersen Granted FDA Breakthrough Therapy Designation for Spinal Muscular Atrophy
Biogen Inc. (Nasdaq: BIIB) has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to salanersen, an investigational antisense oligonucleotide (ASO) being developed for the treatment of spinal muscular atrophy (SMA). The designation is intended to accelerate the development and regulatory review of therapies for serious conditions where early clinical evidence suggests the potential for substantial improvement over existing treatments on clinically meaningful endpoints.
Spinal muscular atrophy is a rare, progressive genetic neuromuscular disorder characterized by the loss of motor neurons in the spinal cord and brainstem, leading to muscle weakness, impaired motor function, and, in severe cases, respiratory failure. Despite advances in treatment over the past decade, significant unmet needs remain, particularly for patients who exhibit suboptimal responses to current gene therapy or other disease-modifying treatments. Against this backdrop, salanersen is being investigated as a next-generation therapeutic option with the potential to deliver durable efficacy through once-yearly dosing.
Salanersen is designed as a novel antisense oligonucleotide that targets the underlying genetic mechanisms of SMA to increase functional survival motor neuron (SMN) protein levels. Unlike currently available therapies that require more frequent dosing schedules, salanersen is being developed with the goal of achieving sustained therapeutic activity with a single annual administration. If successful, this approach could represent a meaningful advancement in treatment convenience, long-term disease control, and patient quality of life.
The FDA’s decision to grant Breakthrough Therapy Designation was supported by emerging clinical data from a Phase 1b study of salanersen. These results were recently presented at two major scientific meetings: the 2026 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference and the 5th International Scientific Congress on SMA (SMA Europe 2026). The data highlighted encouraging signals of both motor function improvement and biological activity in patients previously treated with gene therapy who had demonstrated a suboptimal response.
In the Phase 1b study, children with SMA who had previously received gene therapy were administered once-yearly salanersen. Following treatment initiation, investigators observed clinically meaningful improvements in motor function, including the attainment of critical developmental milestones such as the ability to sit independently and, in some cases, walk. These functional gains are particularly notable given the severity and progressive nature of SMA, as well as the limited recovery typically observed in patients with established motor neuron loss.
In addition to motor improvements, the study also provided evidence suggesting a potential slowing of neurodegeneration. This was assessed through reductions in neurofilament levels, a biomarker associated with neuronal injury and disease activity in neurodegenerative conditions. Lower neurofilament levels observed following treatment with salanersen suggest that the therapy may be impacting the underlying disease process rather than solely addressing symptoms.
Importantly, salanersen was generally well tolerated in the Phase 1b study, with a safety profile consistent with expectations for antisense oligonucleotide therapies. No new or unexpected safety signals were reported, further supporting continued clinical development of the program. While the study was exploratory in nature, the combination of functional improvements, biomarker changes, and tolerability has contributed to growing interest in salanersen’s potential role in the SMA treatment landscape.
Clinical experts in the field have emphasized the significance of the FDA’s decision and the unmet medical need that continues to exist in SMA care. According to Dr. Diana Castro of the Neurology Rare Disease Center in Flower Mound, Texas, the Breakthrough Therapy Designation acknowledges that patients with SMA still require more effective and durable treatment options. She noted that in the Phase 1b study, some children previously treated with gene therapy demonstrated unexpected and meaningful gains in motor function after receiving salanersen, including improvements in sitting and walking abilities. These observations, she said, highlight the potential of the therapy and support continued advancement into later-stage clinical trials.
Patient advocacy groups have also welcomed the FDA’s decision. Kenneth Hobby, President of Cure SMA, noted that the designation reflects both the urgency of unmet needs within the SMA community and the importance of advancing promising therapies through expedited regulatory pathways. He emphasized that while current treatments have significantly changed the SMA landscape, many patients continue to experience disease progression or incomplete responses, underscoring the need for additional therapeutic options.
From a regulatory and development perspective, Biogen views the Breakthrough Therapy Designation as a major milestone for its SMA pipeline. The designation not only provides increased interaction with the FDA during development but also has the potential to accelerate the overall review process if subsequent clinical trials continue to demonstrate strong efficacy and safety outcomes.
According to Stephanie Fradette, Pharm.D., Head of the Rare Neurology Development Unit at Biogen, the FDA’s decision reflects its assessment that salanersen may have the potential to demonstrate substantial improvement over currently available therapies. She described the designation as an important step forward for the company’s SMA portfolio as it advances toward Phase 3 development, where the therapeutic profile of salanersen will be more rigorously evaluated across broader and more diverse patient populations.
The global Phase 3 development program for salanersen is designed to further assess its safety, efficacy, and long-term clinical benefit across multiple SMA patient populations. The program consists of three key studies, each targeting different stages of disease and treatment history.
The first study, STELLAR-1, is currently recruiting and is an open-label trial designed to evaluate salanersen in treatment-naïve and presymptomatic infants diagnosed with SMA. These participants are under six weeks of age and represent a population where early intervention may have the greatest potential to alter disease trajectory and preserve motor neuron function.
The second study, SOLAR, is also currently recruiting and will assess salanersen in adolescents and adults aged 15 to 60 years living with SMA. This study includes both treatment-naïve patients and individuals who have previously been treated with risdiplam, an existing SMA therapy. SOLAR is designed to evaluate the impact of salanersen across a broader, more heterogeneous patient population, including those with longer disease duration.
The third study, STELLAR-2, is a randomized, double-blind, sham-controlled trial expected to begin enrollment in June 2026. This study will evaluate salanersen in infants who received presymptomatic gene therapy with onasemnogene abeparvovec-xioi at six weeks of age or younger. Participants will begin treatment approximately six months after gene therapy administration, allowing researchers to assess salanersen’s potential role as a follow-on or adjunctive therapy in early-treated patients.
Together, these studies are intended to define the clinical profile of salanersen across multiple stages of SMA, from presymptomatic infants to older patients with established disease. The breadth of the program reflects the complexity of SMA and the need for individualized treatment approaches based on disease stage, prior therapy, and functional status.
As the SMA treatment landscape continues to evolve, salanersen represents a potential new class of therapy that could complement or extend existing treatment options. Its once-yearly dosing paradigm, combined with early signals of motor improvement and neurodegenerative slowing, positions it as a candidate of significant interest in the field of rare neurology.
With Breakthrough Therapy Designation now granted, Biogen is expected to work closely with the FDA to expedite the clinical development pathway for salanersen as it advances through Phase 3 trials. The outcome of these studies will ultimately determine whether the therapy can fulfill its early promise and become a meaningful addition to the evolving standard of care for spinal muscular atrophy.
About Salanersen
Salanersen (BIIB115) is a novel, intrathecally administered antisense oligonucleotide (ASO) in development for SMA. Salanersen is designed to correct splicing of SMN2 pre-mRNA to increase production of SMN protein. It has a new chemistry that leads to high potency, enabling the potential for high efficacy with once-yearly dosing.
Salanersen is being evaluated in three global Phase 3 studies designed to evaluate safety and efficacy of 80 mg administered once-yearly in a broad spectrum of individuals living with SMA. Biogen licensed the global development, manufacturing and commercialization rights for salanersen from Ionis Pharmaceuticals, Inc. Salanersen was discovered by Ionis.
Salanersen Phase 1b Study Results
The Phase 1b study included participants (n=24, aged 0.5-12 years), who received at least 2 doses of salanersen (40 mg or 80 mg). The 80 mg dose will be further evaluated in the Phase 3 studies.
In participants who received salanersen 40 mg and 80 mg and had elevated baseline concentrations of neurofilament light chain (NfL), a potential marker of ongoing neurodegeneration, meaningful reductions (75%) in NfL levels were observed at six months; these reductions were sustained throughout the follow-up period. All 24 participants treated with salanersen experienced increases from baseline on one or more endpoints.
Notably, 12 of the 24 achieved at least one new WHO motor milestone, and all participants maintained the motor milestones documented at their baseline. Salanersen has been generally well-tolerated at both 40 and 80 mg doses in the ongoing Phase 1 study, and most adverse events (AEs) have been mild to moderate in severity. As of the analysis, the most common AEs in the 40 mg group were upper respiratory tract infection and vomiting, and the most common AEs in the 80 mg group were pyrexia and upper respiratory tract infection.
About Spinal Muscular Atrophy (SMA)
SMA is a rare, genetic, neuromuscular disease that affects individuals of all ages. It is characterized by a loss of motor neurons in the spinal cord and lower brain stem, resulting in progressive muscle atrophy and weakness.1 SMA is caused by a deficiency in the production of survival motor neuron (SMN) protein due to a damaged or missing SMN1 gene, with a spectrum of disease severity.1 Some individuals with SMA may never sit; some sit but never walk; and some walk but may lose that ability over time.2 In the absence of treatment, children with the most severe form of SMA would usually not be expected to reach their second birthday.1
SMA impacts approximately 1 in 10,000 live births,3-6 is a leading cause of genetic death among infants7 and causes a range of disability in teenagers and adults.2
About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
