Phase 4 Study Shows Stable Motor Function in Adults With SMA on Risdiplam

New 12-month data from the adult cohort of the phase 4 WeSMA study (NCT05232929) suggests that risdiplam (Evrysdi; Genentech) was generally well tolerated in routine clinical practice for the treatment of spinal muscular strophy (SMA), with stable motor function and a safety profile consistent with the pivotal trials.¹

These findings were presented at the 2026 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held September 29 to October 2, in Orlando, Florida, by lead author Sheila Seleri, MD, PhD, executive medical director at Genentech. Year 2 follow-up is expected to further clarify the long-term safety of risdiplam and whether motor stability is maintained in adults with longer disease duration, an area where controlled trial data remain sparse.

For context, risdiplam is an oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved by the FDA for pediatric and adult patients with SMA. Adults account for approximately one-third of the SMA population, a share that continues to grow as disease-modifying therapies extend survival into adulthood, yet real-world evidence on risdiplam in this group remains limited.

The US-based multicenter, longitudinal, prospective, noncomparative study enrolled patients prescribed or continuing risdiplam based on the clinical judgment of their treating physician.² Enrollment closed in December 2024, and assessments occur at baseline, every 6 months in year 1, and once in year 2. The primary end points are the incidences of adverse events (AEs), serious AEs, and AEs of special interest; effectiveness is assessed by change from baseline on the Clinical Global Impression-Change (CGI-C) scale. The data cutoff for this analysis was February 27, 2026.

Of 403 participants enrolled, 170 (42.2%) were adults, and effectiveness data were available for 161 (94.7%). Mean age at enrollment was 35.9 years (SD, 14.3), and 114 (70.8%) were aged 25 years or older. Most participants (n = 134; 83.2%) were established on risdiplam, defined as more than 6 months of use at enrollment, whereas 27 (16.8%) were newly prescribed. Among those with available data, 52.5% had type 2 SMA, 37.5% had type 3 SMA, and 65.0% had 3 SMN2 copies. More than half (55.0%) had previously received nusinersen (Spinraza; Biogen), for a mean of 2.5 years (SD, 1.7).

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In the safety population (N = 170), 79 participants (46.5%) experienced at least 1 AE and 31 (18.2%) experienced a serious AE over 12 months. Eight participants (4.7%) had treatment-related AEs, and 1 (0.6%) had a treatment-related serious AE. Pneumonia and urinary tract infection were the most frequently reported AEs (5.3% each), and pneumonia was also the most common serious AE (4.1%). One participant (0.6%) had an AE of special interest, a potential Hy’s law case. Three participants (1.8%) discontinued risdiplam because of AEs, and no deaths were reported.

At month 12, 47.7% of newly prescribed participants (n = 23) had improved on the CGI-C, 47.8% had no change, and 4.3% had worsened since their last visit. Among those established on risdiplam (n = 115), 47.8% improved, 41.7% had no change, and 10.4% worsened. Motor function remained stable through month 12, with mean changes from baseline of −0.9 points (SD, 4.3) on the Hammersmith Functional Motor Scale–Expanded (HFMSE) and 0.0 points (SD, 2.9) on the Revised Upper Limb Module (RULM) among participants with available data.¹

Controlled data in adults remain limited. The pivotal phase 3 SUNFISH (NCT02908685) trial, which enrolled 180 patients aged 2 to 25 years with type 2 or nonambulant type 3 SMA, showed a 1.55-point treatment difference on the 32-item Motor Function Measure at 12 months favoring risdiplam; exploratory subgroup analyses suggested motor function generally improved in younger patients and stabilized in older patients.³

As a single-arm, noncomparative study, WeSMA lacks a control group, and outcomes may be influenced by prior or concomitant SMA therapies. Not every participant completed each assessment, and motor function testing was optional; at month 12, HFMSE data were available for 31 participants and RULM data for 72. Participants also had heterogeneous baseline characteristics and disease severity, and the newly prescribed subgroup was small. The study is industry sponsored, and all authors are Genentech employees. In addition, CGI-C is a global clinician-rated measure that may be less sensitive than disease-specific motor scales.¹

Risdiplam was first approved by the FDA in August 2020 for adults and children 2 months and older,⁴ and a 5-mg tablet formulation was approved in February 2025 for patients aged 2 years and older weighing more than 20 kg.⁵ The approval is supported by findings of 2 clinical trials in risdiplam’s development, the FIREFISH (NCT02913482) and SUNFISH studies, both of which demonstrated the efficacy of the SMN2-directed RNA splicing modifier in this patient population.

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REFERENCES
1. Seleri S, Lim E, Keto E, Shah R, Shapouri S. A long-term follow-up study of risdiplam (WeSMA study): 12-month results in adult participants with SMA. Presented at: 2026 AANEM Annual Meeting; September 29-October 2, 2026; Orlando, FL. Abstract 262.
2. Long-term follow-up study of risdiplam in participants with spinal muscular atrophy (SMA) (WeSMA). ClinicalTrials.gov identifier: NCT05232929. Updated July 15, 2026. Accessed September 29, 2026. https://clinicaltrials.gov/study/NCT05232929
3. Mercuri E, Deconinck N, Mazzone ES, et al. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2022;21(1):42-52. doi:10.1016/S1474-4422(21)00367-7
4. PTC Therapeutics announces FDA approval of Evrysdi (risdiplam) for the treatment of spinal muscular atrophy in adults and children 2 months and older. News release. PTC Therapeutics. August 7, 2020. Accessed September 29, 2026. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-approval-evrysditm-risdiplam
5. FDA approves Genentech's Evrysdi tablet as first and only tablet for spinal muscular atrophy (SMA). News release. Genentech. February 12, 2025. Accessed September 29, 2026. https://www.gene.com/media/press-releases/15052/2025-02-12/fda-approves-genentechs-evrysdi-tablet-a