The study design of the phase 3 STELLAR trials, presented at the 2026 MDA Conference, aims to investigate salanersen among presymptomatic infants with spinal muscular atrophy.
Researchers recently presented the study design of 2 linked phase 3 trials, STELLAR-1 (NCT07221669) and STELLAR-2 (NCT07444450), which will assess salanersen (Biogen), an intrathecally administered antisense oligonucleotide, in presymptomatic infants with spinal muscular atrophy (SMA). The studies will offer insights on outcomes in infants receiving presymptomatic treatment with salanersen monotherapy, onasemnogene abeparvovec (Zolgensma; Novartis) monotherapy, or onasemnogene abeparvovec followed by salanersen.1,2
Lead author
STELLAR-1 is an open-label, single-arm trial assessing salanersen in treatment-naive, presymptomatic infants aged 6 weeks or younger with SMA and 2 or 3 copies of the survival motor neuron 2 (SMN2) gene. In the study, participants will receive an 80-mg annual dose of salanersen across the 5-year trial period. The primary end points evaluate the attainment of World Health Organization (WHO) motor milestones that are typically unexpected without treatment which include sitting unsupported at the 12-month follow-up for participants with 2 SMN2 copies, and walking independently at the 18-month follow-up for participants with 3 SMN2 copies.
STELLAR-2 is a randomized, double-blind, sham-controlled trial investigating salanersen in infants with SMA and 2 copies of the SMN2 gene who received treatment with onasemnogene abeparvovec (Zolgensma; Novartis) when aged 6 weeks or younger. Participants will be randomized 6 months after receiving onasemnogene abeparvovec to receive active treatment (an 80-mg annual dose of salanersen) or a sham control. Following the 12-month controlled period, patients in the sham control arm will transition to active treatment. Key efficacy end points will include differences in plasma neurofilament light chain levels, motor function scales, and electrophysiology findings between groups at the 12-month and 5-year follow-ups.
In the roundtable series, experts Diana Bharucha-Goebel, MD, and Bakri Elsheikh, MBBS, FRCP, explore the rapidly evolving landscape of SMA care. Across 7 episodes, they cover the latest treatment options, updated best practices, and the growing importance of newborn screening and early diagnosis.
READ MORE:
The initiation of these phase 3 trials follows
The phase 1 single-ascending dose trial featured 2 parts: Part A, a randomized and placebo-controlled segment in health adult male volunteers and Part B, an open-label segment in pediatric patients with SMA previously on onasemnogene abeparvovec. The interim data update, which included 24 patients from Part B, showed that 40 mg and 80 mg doses of salanersen was well tolerated, with most adverse events mild to moderate in severity.
Interim findings from the study revealed that patients on the antisense agent had a 70% mean reduction in neurofilament light, a biomarker of neuroaxonal damage, over the 6-month period, which was sustained through the 1-year dosing interval. Presented at the 2025 SMA Research & Clinical Care Meeting, hosted by
The released data also featured a subgroup of patients, aged 2-12 years, with at least 1 year of follow-up time who received 40 mg of salanersen. Among this group (n = 8), half (n = 4) of the patients achieved new WHO motor milestones that they previously could not achieve on their own or required assistance to do, such as walking, crawling, standing, or sitting. Improvements in motor function were also observed, reflected by a 3.3-point mean change (SD, 4.46) in Hammersmith Functional Motor Scale-Expanded and a 5.3-point improvement in Revised Upper Limb Module.
