FDA grants salanersen Breakthrough Therapy status, an early step for Biogen's investigational once-yearly SMA drug

Biogen said on June 4 that the U.S. Food and Drug Administration has granted Breakthrough Therapy Designation to salanersen, an investigational antisense drug for spinal muscular atrophy (SMA) that the company is developing for once-yearly intrathecal dosing. The designation is a procedural status that lets the FDA work more closely with a sponsor; it is not an approval, and it does not establish that the drug works.

Salanersen (also known as BIIB115) uses the same basic strategy as Biogen’s approved drug nusinersen (Spinraza): an antisense oligonucleotide delivered into the spinal fluid, designed to correct splicing of the SMN2 gene’s pre-mRNA and raise production of survival motor neuron (SMN) protein. The pitch for the successor molecule is convenience. Under its FDA label, nusinersen maintenance is dosed once every four months — three lumbar punctures a year. Biogen is targeting one dose a year for salanersen, though that regimen is a development goal for an in-trial drug, not an approved schedule.

What the early data are — and are not

Biogen attributes its efficacy signals to what it calls a Phase 1b study: an open-label, single-arm cohort of 24 children aged 0.5 to 12 years who had previously received the gene therapy onasemnogene abeparvovec (Zolgensma) and had a suboptimal response. In its June 4 release, the company reports that 12 of the 24 achieved at least one new World Health Organization (WHO) motor milestone, that all 24 showed increases from baseline on one or more endpoints, and that neurofilament light chain (NfL) fell 75% at six months.

Three caveats are essential. First, those numbers are company-reported and described by Biogen itself as an exploratory analysis; they have not appeared in a peer-reviewed paper. Second, the cohort is open-label, single-arm and uncontrolled — with no comparator, the milestone and motor-function changes cannot be separated from natural history or from the prior gene therapy. Third, NfL is a surrogate biomarker of nerve-cell damage, not a measure of clinical benefit; a fall in NfL is not the same as a proven improvement in survival or function.

Biogen reports that 12 of 24 children gained a new motor milestone and that NfL fell 75% at six months — but these are exploratory, uncontrolled, company-stated figures, not peer-reviewed efficacy and not a clinical-benefit endpoint.

The registered early-phase study on ClinicalTrials.gov, NCT05575011, is broader than that pediatric read-out. It is a Phase 1 trial with planned enrollment of 62, combining a randomized, placebo-controlled single-ascending-dose arm in healthy adult male volunteers (Part A) with an open-label, multiple-ascending-dose arm plus long-term extension in post-gene-therapy pediatric SMA participants (Part B). Its registered primary endpoint is safety — adverse events and serious adverse events — with pharmacokinetics in cerebrospinal fluid and serum as the secondary measures. No results have been posted to the registry, and the study is not finished: its registered primary completion date is in November 2031, reflecting that long-term extension. Biogen has not stated on the registry how its “Phase 1b” n=24 figures map onto this study’s Part B.

The pivotal program is only now starting

The confirmatory evidence is years away. The registry lists three Phase 3 trials. STELLAR-1 (NCT07221669) is an open-label study in presymptomatic infants, now recruiting, with co-primary efficacy endpoints: the share of infants with two SMN2 copies sitting unsupported at 12 months, and of those with three copies walking alone at 18 months. SOLAR (NCT07444476) is an open-label study in people aged 15 to 60 who are treatment-naive or previously on risdiplam, also recruiting, with a primary endpoint of change from baseline on the Hammersmith Functional Motor Scale–Expanded at 12 months in the treatment-naive cohort. STELLAR-2 (NCT07444450) is a randomized, double-blind, sham-controlled study in infants after gene therapy, not yet recruiting, whose registered primary endpoint is safety. Registered primary completion dates run from June 2028 (SOLAR) and November 2028 (STELLAR-1) into July 2029 (STELLAR-2).

Until those read-outs, the case for salanersen is a dosing-burden argument supported by early, exploratory, uncontrolled data — not a confirmed efficacy win.