Salanersen (BIIB115) for improving movement in people 15–60 with spinal muscular atrophy who are treatment‑naïve or previously on risdiplam

An Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Salanersen (BIIB115) in Participants Aged 15-60 Years With Spinal Muscular Atrophy Who Are Either Treatment-Naïve or Have Previously Been Treated With Risdiplam

This trial tests whether salanersen helps movement and is safe for people aged 15 to 60 with spinal muscular atrophy who are either new to treatment or have taken risdiplam.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 15 Years to 60 Years
• Sex: All
• Sponsor: Biogen (Industry-sponsored)
• Locations: 1 site (Norfolk, Virginia)
• Trial ID: NCT07444476 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional study enrolls participants aged 15–60 with genetically confirmed 5q SMA and a baseline HFMSE score between 10 and 54, including both ambulatory and nonambulatory patients. Participants are split into two cohorts based on prior exposure to SMA therapy: treatment‑naïve or previously treated with risdiplam, and will receive salanersen with monitoring of motor function, safety, tolerability, and pharmacokinetics. The primary endpoint focuses on clinical efficacy for movement using standardized motor scales, while secondary endpoints capture adverse events and PK parameters. The protocol excludes prior myostatin inhibitor use and requires the ability to sit unassisted for at least 10 seconds and, for ambulatory participants, the capacity to complete a 6‑minute walk test at screening.

Who should consider this trial

Good fit: Ideal candidates are people aged 15–60 with genetically confirmed 5q SMA, SMN2 copy number ≥1, baseline HFMSE 10–54, able to sit unassisted for ≥10 seconds, and who are either treatment‑naïve or previously treated with risdiplam and not on myostatin inhibitors.

Not a fit: People outside the 15–60 age range, with HFMSE scores below 10 or above 54, with different genetic diagnoses, or currently using myostatin inhibitors are unlikely to qualify or derive benefit from this protocol.

Why it matters

Potential benefit: If successful, salanersen could improve motor function and daily mobility by increasing functional SMN protein production from the SMN2 gene.

How similar studies have performed: Other SMN‑enhancing therapies such as nusinersen, risdiplam, and gene replacement have demonstrated clinical benefit, but salanersen is a different investigational approach and has less established evidence in this adolescent and adult population.

Eligibility criteria

Key Inclusion Criteria:

* Participants aged 15 to 60 years, inclusive, at the time of informed consent
* Participants with genetic documentation of 5q Spinal Muscular Atrophy (SMA) (homozygous gene deletion or mutation or compound heterozygous mutation).
* Participants with clinical signs and symptoms consistent with SMA.
* Survival motor neuron 2 (SMN2) copy number ≥ 1.
* Participants with baseline Hammersmith Functional Motor Scale - Expanded (HFMSE) total score of ≥ 10 to ≤ 54.
* Participants who are able to sit without using support for at least 10 seconds.
* Participants with no prior treatment with myostatin inhibitors and a willingness to remain off concurrent myostatin inhibitor therapy for the duration of the study.
* Ambulatory and nonambulatory participants:

  * Ambulatory participants must be able to walk at least 10 meters independently without assistance and are willing and able to complete the 6 Minute Walk Test (6MWT) at Screening.
* For participants in the treatment-naïve cohort:

  * No prior treatment with an approved SMA Disease Modifying Therapy (DMT) or an investigational drug given for the treatment of SMA.
* For participants in the risdiplam-treated cohort:

  * Currently receiving risdiplam treatment and have been on once-daily 5 milligrams (mg) risdiplam treatment for at least 6 months prior to Screening.
  * Willing to stop risdiplam therapy for the duration of the study. The last dose of risdiplam must be taken the day before the first dose of salanersen.
  * No prior treatment with nusinersen, onasemnogene abeparvovec-xioi/onasemnogene abeparvovec-brve (OA), other approved DMTs for SMA or investigational drugs given for the treatment of SMA apart from risdiplam.

Key Exclusion Criteria:

* Respiratory insufficiency at Screening, defined by the medical necessity for invasive or noninvasive ventilation for \> 6 hours during a 24-hour period (except for nocturnal bilevel positive airway pressure).
* Medical necessity for a gastric feeding tube, where the majority of nutrition is provided by this route, as assessed by the site Investigator at Screening.
* History of brain or spinal cord disease or other contraindications (e.g., severe scoliosis) that would interfere with the lumbar puncture (LP) procedures, Cerebrospinal fluid (CSF) circulation, efficacy assessments, or safety assessments (including a history of hydrocephalus or implanted shunt for CSF drainage), as assessed by the Investigator.
* Hospitalization for surgery, a pulmonary event, or nutritional support within 2 months prior to Screening or plans to undergo elective procedures or surgeries at any time after signing the Informed Consent Form (ICF) through the end of the study. Note: If prior scoliosis surgery has been performed, it must be done at least 1 year prior to Screening.
* Presence of an active medical issue (e.g., infection, recent fracture) that would make the participant unsuitable for inclusion, as assessed by the Investigator.
* Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 90 days or 5 half-lives of the treatment (if known), whichever is longer, prior to Screening. This includes neuromodulation therapy such as spinal cord stimulation.

Note: Other protocol-defined inclusion/exclusion criteria will apply.

Where this trial is running

Norfolk, Virginia

• Childrens Hospital of the Kings Daughter Norfolk — Norfolk, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: US Biogen Clinical Trial Center

Conditions Spinal Muscular Atrophy