Phase 3 Open‑Label Study of Intrathecal BIIB115 in Patients Aged 15–60 Years with Spinal Muscular Atrophy, Treatment‑Naïve or Previously Treated with Risdiplam

The primary objective is to assess the clinical efficacy of salanersen in participants with Spinal Muscular Atrophy who are either treatment‑naïve or have previously received risdiplam, thereby determining the therapeutic impact on motor outcomes. The secondary objective is to evaluate the safety profile, tolerability, and pharmacokinetic characteristics of salanersen in the same population.

The trial enrolled 50 individuals diagnosed with Spinal Muscular Atrophy (SMA), ages 15 to 60 years inclusive, comprising both male and female participants. Subjects were selected based on confirmed 5q SMA genetic status, SMN2 copy number ≥ 1, and a baseline score of 10–54 on the Hammersmith Functional Motor Scale – Expanded. Both ambulatory and non‑ambulatory participants were eligible; ambulatory subjects were required to walk at least 10 m independently and to complete a 6 Minute Walk Test at screening. Inclusion required the ability to sit unsupported for at least 10 seconds and the absence of prior myostatin‑inhibitor therapy or other disease‑modifying treatments, except for a cohort receiving risdiplam for ≥ 6 months who agreed to discontinue it before the first dose of salanersen. Participants in the treatment‑naïve cohort had no history of approved SMA disease‑modifying therapy or investigational SMA drugs. The study population included vulnerable individuals as defined by the protocol and represented the patient group for SMA.

The study is an open‑label, Phase 3 investigation of the intrathecal administration of Spinal Muscular Atrophy therapy Salanersen (BIIB115) at a dose of 80 mg in a solution for injection, enrolling participants aged 15–60 years who are either treatment‑naïve or have been receiving risdiplam for at least six months. The design is a single‑arm, controlled evaluation of efficacy and safety with a planned overall duration of up to five years (Day 1825) for each participant, including a primary efficacy assessment at Month 12. The sequence of study visits includes a screening visit to confirm eligibility (genetic confirmation of 5q SMA, baseline HFMSE score, ambulation criteria, and required washout of risdiplam), a baseline visit on Day 0 for the first intrathecal dose, regular follow‑up visits for safety monitoring, pharmacokinetic sampling, and functional assessments (HFMSE, Revised Upper Limb Module, 6‑Minute Walk Test, CMAP, patient‑reported outcomes) conducted at predefined intervals through Month 12 and subsequently at scheduled intervals up to Day 1825, and a final end‑of‑study visit to collect long‑term outcome data and conclude study participation. Participant involvement therefore spans from the initial screening through the final visit, with a maximum exposure period of approximately five years.

The investigational product, designated BIIB115, is supplied as a SOLUTION FOR INJECTION intended for intrathecal administration. Each dose contains 80 mg of the active substance. The medication is administered by a single lumbar puncture at a frequency defined by the study protocol, with dosing intervals and total treatment duration specified in the investigator’s manual. The formulation is prepared under aseptic conditions immediately prior to administration.

No placebo or active comparator is incorporated in this open‑label trial. Participants receive only the investigational medication; concomitant standard‑of‑care therapies may be continued at the discretion of the treating clinician in accordance with local practice and documented in the case report form.

Drug administration is performed by qualified personnel using sterile technique. Dosing schedules are recorded in the trial database, and compliance is monitored through source document verification, infusion logs, and periodic assessment of drug accountability. Any deviations from the prescribed regimen are reported according to the trial’s safety monitoring procedures.

Efficacy in the study of salanersen for participants with Spinal Muscular Atrophy is evaluated using motor function and functional capacity measures. The primary efficacy parameter is the change from baseline in the total score of the Hammersmith Functional Motor Scale – Expanded (HFMSE) in the treatment‑naïve cohort, assessed at month 12. The HFMSE assesses 33 motor items, each scored to produce a total ranging from 0 to 66, with higher scores indicating better motor ability.

Secondary efficacy assessments include:

• Proportion of participants achieving a ≥ 3‑point increase in HFMSE total score (up to Day 1825).
• Proportion achieving a ≥ 2‑point increase in Revised Upper Limb Module (RULM) total score (up to Day 1825). The RULM comprises 20 items scored 0–37.
• Proportion of ambulatory participants with a ≥ 30‑meter improvement in 6‑Minute Walk Test (6MWT) distance (up to Day 1825).
• Change from baseline in HFMSE total score (up to Day 1825).
• Change from baseline in RULM total score (up to Day 1825).
• Change from baseline in total 6MWT distance for ambulatory participants (up to Day 1825).
• Change from baseline in Compound Muscle Action Potential (CMAP) amplitudes for ulnar‑abductor digiti minimi and peroneal‑tibialis anterior nerve‑muscle pairs (up to Day 1825).
• Patient Global Impression of Change (PGI‑C) score, a 7‑point self‑report scale (up to Day 1825).
• Change from baseline in SMA Independence Scale – Upper Limb Module (SMAIS‑ULM) total score (up to Day 1825).

All assessments employ validated instruments and are performed at baseline and at scheduled follow‑up visits according to the specified time frames. Data are analyzed by comparing change from baseline values and by calculating the proportion of participants meeting predefined response thresholds.