FDA
Gene therapy approved for spinal muscular atrophy
Brand name: Itvisma
Generic name: onasemnogene abeparvovec-brve
Manufacturer: Novartis
Approval date: November 24, 2025
FDA approved Itvisma (onasemnogene abeparvovec-brve) for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients ≥2 years of age with confirmed mutation in the survival motor neuron 1 (SMN1) gene. Itvisma is an adeno-associated virus (AAV) vector-based gene therapy.
Efficacy
Itvisma demonstrated substantial evidence of effectiveness for the treatment of SMA in pediatric patients ≥2 years of age with a confirmed mutation in the SMN1 gene based on primary evidence of effectiveness from the phase 3 STEER study (NCT05089656), and the confirmatory evidence of effectiveness from data characterizing the mechanism of the product’s action, as well as efficacy findings from Zolgensma (onasemnogene abeparvovec-xioi) which contains the same active ingredient in an IV formulation. The applicant provided adequate justification to support expanding the indication beyond the pivotal study population to include adult patients with SMA, however, warnings and precautions are warranted due to the potentially increased risks of adverse events of special interest (e.g., hepatotoxicity and cardiotoxicity) in adult patients with preexisting chronic medical conditions.
The active ingredient in Itvisma is identical to Zolgensma but formulated at a different concentration. Zolgensma is administered IV based on patient weight to pediatric patients <2 years of age with SMA due to bi-allelic mutations in the SMN1 gene. Itvisma is a concentrated formulation in a smaller delivery volume, administered directly to the CNS via a single intrathecal injection independent of patient weight, which expands treatment options available to patients with SMA >2 years of age.
The direct administration of Itvisma into the CSF allows for delivery to motor neurons with a lower dose of vector, without the need to adjust for the patient’s body weight. This provides a treatment with rapid onset and direct targeting of the genetic root cause of SMA. By addressing the root cause of SMA, Itvisma restores SMN protein production and halts further disease progression.
Safety
The FDA review team worked collaboratively to leverage Zolgensma safety data and most of the side effects of Itvisma are consistent with identified risks associated with Zolgensma. Information from the hepatotoxicity boxed warning in the Zolgensma label is retained in the Itvisma label with appropriate modifications. This approach is supported by clinical data showing hepatotoxicity in Itvisma clinical studies.
The most common adverse reactions (≥10% of patients) include upper respiratory tract infection, upper GI symptoms, pyrexia, and headache.
Sources:
FDA Approves Gene Therapy for Treatment of Spinal Muscular Atrophy. [News release]. 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-gene-therapy-treatment-spinal-muscular-atrophy
Itvisma (onasemnogene abeparvovec-brve) [package insert]. Novartis. https://www.novartis.com/us-en/sites/novartis_us/files/Itvisma.pdf Revised November 2025. Accessed November 26, 2025.
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]. 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