FDA Approves New Intrathecal Administration Route for Spinal Muscular Atrophy Gene Therapy

According to a new announcement, the FDA has approved an intrathecal formulation of Novartis’ onasemnogene abeparvovec-brve, a gene therapy indicated for children, teens, and adults with spinal muscular atrophy (SMA). Marketed as Itvisma, the medication becomes the first intrathecally administered treatment for SMA, giving patients a new optional route of administration.¹

The gene therapy, approved for a broad SMA population, is designed to address the genetic root cause of SMA by providing a functional copy of the human SMN1 gene to improve motor function through sustained survival motor neuron (SMN) protein expression. An adeno-associated, virus vector-based medication, onasemnogene abeparvovec was originally approved in 2019 as a single intravenous infusion for a broad range of SMA.

The FDA’s latest decision to approve the intrathecal formulation was based on positive data from the phase 3 STEER study (NCT05089656) as well as supportive findings from the ongoing phase 3b STRENGTH study (NCT05386680). STEER, the most notable of the trials, met its primary end point, as treatment with the intrathecal formulation led to significant enhancements in motor function, assessed through total Hammersmith Functional Motor Scale-Expanded (HFMSE) scores.

"The FDA’s approval of intrathecal onasemnogene abeparvovec is a game-changing advance, expanding the use of transformational gene replacement therapy for SMA across age groups,” John Day, MD, PhD, professor of neurology and pediatrics, director, Division of Neuromuscular Medicine, Stanford University School of Medicine, and co-director, Stanford’s Neuro IGNITE Center, said in a statement.¹ "This achievement is not only a significant step forward for SMA – it also signals new possibilities for the broader field of neurological disorders and genetic medicine."

STEER, a 52-week study, comprised 126 treatment-naïve patients with SMA Type 2 who were randomly assigned 1:1 to either Itvisma or sham procedure, followed by a crossover phase. In the trial, those on the intrathecal medication demonstrated a statistically significant 2.39-point improvement on HFMSE vs 0.51 points for those on sham (P = .0074). All secondary end points consistently favored Itvisma, despite not achieving statistical significance due to the pre-planned multiple testing procedure.²

"This new route of administration for a single dose of gene replacement therapy can mean so much more than what is measured by numbers on a functional motor scale – it could mean greater independence and freedom in activities of daily life," Kenneth Hobby, president at Cure SMA, said in a statement.¹ "The SMA disease landscape has dramatically changed over the last six years, when the first gene therapy was approved. This is another welcome advancement, and it represents real progress in expanding access for many older patients and addressing the unmet needs that remain in our community."

READ MORE: FDA Adds Boxed Warning, Narrows Indication for DMD Gene Therapy

STRENGTH differed slightly from STEER in that it tested safety, tolerability, and efficacy of the intrathecal medication in patients with SMA who discontinued previously approved treatments nusinersen (Spinraza; Biogen) or risdiplam (Evrysdi; Genentech). The open-label, single-arm study included 27 patients with a mean age of 7.4 years and were on risdiplam or nusinersen for a mean duration of 2.98 and 4.32 years, respectively.

Presented earlier this year at the Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, Itvisma continued to maintain a similar safety profile that was observed in STEER. Over the 52-week period, patients on the treatment demonstrated a least square mean increase of 1.05 points in HFMSE, considered a stabilization. The most frequent adverse events (AEs) were common cold, pyrexia, and vomiting, with 13 patients (48.1 percent) experiencing treatment-related events, and no adverse events led to death or study discontinuation.²

Although it wasn’t part of the approval package, intrathecal onasemnogene abeparvovec was tested in another study dubbed STRONG (NCT03381729). This trial included 23 sitting, nonambulatory patients with SMA testing three dose levels across two age groups (6 to <24 months and 24 to <60 months). After 12 months, older patients in the medium-dose cohort (1.2 x 10¹⁴ vg) showed significant improvements in HFMSE scores compared with historical controls, reaching roughly twice the accepted minimal clinically meaningful difference (P <.01).³

Additional findings indicated that OAV101IT was generally safe, with no deaths reported and all participants experiencing at least one treatment-emergent adverse event, most commonly upper respiratory infection, pyrexia, cough, vomiting, and constipation. Although younger patients did not achieve the primary end points of standing or walking independently, gains were seen in Bayley-III motor subtests, though the lack of natural history data for type 2 SMA makes it difficult to determine whether these improvements reflect development or treatment effect.

REFERENCES
1. Novartis receives FDA approval for Itvisma®, the only gene replacement therapy for children two years and older, teens, and adults with spinal muscular atrophy (SMA). News release. Novartis. November 24, 2025. Accessed November 24, 2025. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-itvisma-only-gene-replacement-therapy-children-two-years-and-older-teens-and-adults-spinal-muscular-atrophy-sma
2. New Novartis Phase III data demonstrate meaningful efficacy and safety results of intrathecal onasemnogene abeparvovec in broad patient population with SMA. News release. Novartis. March 19, 2025. Accessed November 24, 2025. https://www.novartis.com/news/media-releases/new-novartis-phase-iii-data-demonstrate-meaningful-efficacy-and-safety-results-intrathecal-onasemnogene-abeparvovec-broad-patient-population-sma
3. Finkel RS, Darras BT, Mendell JR, et al. Intrathecal Onasemnogene Abeparvovec for Sitting, Nonambulatory Patients with Spinal Muscular Atrophy: Phase I Ascending-Dose Study (STRONG). J Neuromuscul Dis. 2023;10(3):389-404. doi:10.3233/JND-221560