FDA Approves Itvisma, a New Intrathecal Route for Novartis’ SMA Gene Therapy

The FDA has approved Novartis’ onasemnogene abeparvovec-brve (also known as OAV101 IT), an intrathecally-delivered version of the separately marketed gene therapy onasemnogene abeparvovec (Zolgensma), for the treatment of spinal muscular atrophy (SMA) in people 2 years of age and older who have a confirmed mutation in the survival motor neuron 1 (SMN1) gene.¹ It is to be marketed under the name Itvisma.

According to Novartis, it is the first gene replacement therapy to have been approved “for this broad population.”¹ It uses a fixed dose that does not require adjustment for age or weight, and is intended as a 1-time treatment.

“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 W. Day, MD, PhD, a professor of neurology and pediatrics, the director of the Division of Neuromuscular Medicine at Stanford University School of Medicine, and codirector of 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.”

The FDA’s decision was based on data from the phase 3 STEER clinical trial (NCT05089656) and the open-label phase 3b STRENGTH clinical trial (NCT05386680). Data from STEER, which evaluated the therapy against a placebo in treatment-naive children aged 2 to less than 18 years who could sit but had not ever walked independently, were presented earlier this year at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas.^1,2 It was found that patients who received the gene therapy (n = 75) achieved a 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE), whereas those who received the placebo (n = 51) showed only a 0.51 point improvement on the HFMSE (P = .0074); as such, STEER met its primary end point. Novartis noted that results for the secondary end points did not reach statistical significance because of the preplanned multiple testing procedure, but that these findings “consistently favor” Itvisma.

With regard to safety, adverse events (AEs) reported across STEER and STRENGTH were consistent.¹ Upper respiratory tract infection and pyrexia constituted the most common AEs in STEER and cold, pyrexia, and vomiting constituted the most common AEs in STRENGTH.

“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, the president of Cure SMA, added to the statement.¹ “The SMA disease landscape has dramatically changed over the last 6 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.”

Novartis stated that Itvisma will become available in the United States in December 2025 and that patients and providers can contact Novartis Patient Support for help. Although both Itvisma and Zolgensma utilize an adeno-associated virus 9 vector, Itvisma is differentiated by the fact that it is delivered directly to the spine, whereas Zolgensma is delivered systemically.²

A few months before MDA’s conference this year, CGTLive® spoke to Barry J Byrne, MD, PhD, the chief medical advisor of MDA and a physician-scientist at the University of Florida, about what he was looking forward to at the meeting. Byrne highlighted SMA and muscular dystrophy as disease areas where he expected to see notable advances.

“Really, this is the era of therapies for neuromuscular diseases,” Byrne told CGTLive. “In the past year, we saw an additional few strategies that are transformative in the care of boys with Duchenne muscular dystrophy and we have continued to make advances in SMA care following on the enormous success of the release of Zolgensma in 2019. There are now more than 3,000 patients who've received that gene therapy product, and we'll see more new ideas about gene therapy strategies for both central nervous system disorders, as well as muscle disorders that affect this population.”

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 25, 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. March 19, 2025. Accessed November 25, 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