FDA Approves Gene Therapy for Spinal Muscular Atrophy in Patients Aged 2 Years and Older
Key Clinical Summary
- The US Food and Drug Administration (FDA) has approved onasemnogene abeparvovec-brve (Itvisma) for treatment of spinal muscular atrophy (SMA) in pediatric and adult patients aged 2 years and older with confirmed SMN1 mutation.
- Onasemnogene abeparvovec-brve is administered as a one-time intrathecal injection, delivering the therapeutic gene directly to the central nervous system regardless of patient age or body weight.
- Phase 3 clinical data demonstrated improved motor function and stabilization of disease irrespective of prior treatment history, making onasemnogene abeparvovec-brve the first gene replacement therapy for SMA across a broad age range.
The FDA granted approval to onasemnogene abeparvovec-brve (Itvisma) on November 24, 2025, extending gene therapy to children older than 2, teens, and adults with spinal muscular atrophy (SMA). The therapy, developed by Novartis, is a one-time, intrathecal, gene-replacement injection available to much broader patient populations than onasemnogene abeparvovec-xioi (Zolgensma), which is indicated for children under 2 years old.
Regulatory Decision
Onasemnogene abeparvovec-brve uses an adeno-associated virus (AAV) vector to deliver a functional copy of the SMN1 gene directly into the cerebrospinal fluid via a single intrathecal injection — a fixed-dose regimen independent of patient weight.
The approval was based on substantial evidence from the Phase 3 STEER study and further supported by the open-label Phase 3b STRENGTH study. This evidence was further supplemented by mechanistic data and long-term outcomes from the study of onasemnogene abeparvovec-xioi, which contains the same active ingredient in an intravenous formulation.
Because direct intrathecal delivery allows for a lower vector dose and more concentrated delivery to motor neurons, the formulation avoids the weight-based dosing constraints of prior intravenous therapy, facilitating use across a heterogeneous patient population
The FDA retained boxed warnings related to hepatotoxicity and cardiotoxicity, particularly cautioning in adults with preexisting chronic conditions.
Clinical Implications
The approval of onasemnogene abeparvovec-brve represents a landmark advancement in SMA care. For the first time, gene replacement therapy is accessible to older children, adolescents, and adults — populations previously ineligible for such treatment. This expansion offers potential to alter disease trajectory by restoring SMN protein production, halting further motor neuron loss, and possibly improving—or stabilizing—motor function.
The convenience of a one-time intrathecal administration simplifies logistics and may reduce burden compared with chronic or repeated treatments. Additionally, the fixed-dose regimen independent of weight could standardize care delivery across diverse clinical settings.
However, clinicians must carefully evaluate patients’ liver and cardiac status before treatment, particularly in adults with comorbidities, given the retained safety warnings. Long-term monitoring will be essential to assess durability of benefit and late-onset adverse events.
Expert Commentary
“Significant unmet need remains in SMA, particularly for patients across various ages and motor function levels, predominantly those 2 years of age and older,” said Vijay Kumar, MD, Acting Director, Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research. “This approval shows our continued commitment to supporting and facilitating treatments for patients with rare diseases.”
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