FDA Approves Itvisma®: A Landmark Gene Therapy for SMA

In a pivotal advancement for rare disease treatment, the U.S. Food and Drug Administration (FDA) has approved Itvisma® (onasemnogene abeparvovec-brve), developed by Novartis, as the first and only gene replacement therapy for children aged 2 years and older, teens, and adults with spinal muscular atrophy (SMA). Announced on November 24, 2025, this approval expands access to a one-time, intrathecal (spinal) infusion that targets the genetic root cause of SMA, potentially transforming care for a population previously limited to chronic therapies.

Understanding SMA: A Devastating Genetic Disorder

Spinal muscular atrophy (SMA) is a rare, inherited neuromuscular disease caused by mutations or deletions in the survival motor neuron 1 (SMN1) gene, which encodes a protein essential for motor neuron survival and function. Without functional SMN1, motor neurons degenerate, leading to progressive muscle weakness, loss of motor function, and challenges with breathing, swallowing, and daily activities. SMA affects approximately 1 in 10,000 live births, with around 9,000 individuals living with the condition in the U.S. alone. Historically, untreated SMA has been the leading genetic cause of infant mortality, though early interventions have improved outcomes.

Prior to this approval, gene therapy options like Novartis’ Zolgensma (the intravenous formulation of the same active ingredient) were restricted to infants under 2 years old. Older patients relied on chronic treatments such as nusinersen (Spinraza) or risdiplam (Evrysdi), which require ongoing administration and do not address the genetic defect directly. Itvisma fills this gap by delivering a functional copy of the SMN1 gene via an adeno-associated virus (AAV9) vector directly into the central nervous system, enabling sustained SMN protein production without dose adjustments for age or weight.

Why This Approval Matters: A Shift from Chronic to Curative Care

This milestone is monumental for several reasons. First, it democratizes gene therapy for nearly the entire SMA population, offering a fixed-dose, one-time treatment that could reduce the treatment burden and improve long-term motor function. “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,” said Kenneth Hobby, President of Cure SMA.

Second, the approval underscores the maturation of gene therapy technologies. Itvisma’s intrathecal delivery bypasses some limitations of intravenous methods, potentially enhancing efficacy in older patients with established disease progression. Novartis projects peak sales in the multibillion-dollar range, reflecting its potential to treat thousands more patients globally.

The therapy carries a wholesale acquisition cost of $2.59 million, slightly higher than Zolgensma’s $2.5 million, but Novartis offers patient support programs for access and financial assistance. Itvisma is expected to launch in the U.S. in December 2025.

Evidence from Phase III Trials: Rigorous Validation of Efficacy and Safety

The FDA’s decision was grounded in robust data from two pivotal Phase III studies: the registrational STEER trial (NCT05089656) and the supportive open-label STRENGTH trial (NCT05386680). These trials enrolled patients aged 2 and older with confirmed bi-allelic SMN1 mutations, including those with prior treatment exposure, providing comprehensive evidence across disease severities.

STEER Trial Highlights

The double-blind, placebo-controlled STEER study evaluated 126 ambulatory and non-ambulatory participants (aged 2–21 years). Patients received a single intrathecal dose of Itvisma or placebo. The primary endpoint was change from baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) score at week 52, a validated measure of motor function.

• Motor Function Improvement: Itvisma-treated patients (n=75) showed a statistically significant mean improvement of 2.39 points on the HFMSE, compared to just 0.51 points in the placebo group (n=51; P=0.0074). This gain equates to clinically meaningful enhancements, such as improved ability to stand or walk short distances.
• Stabilization Over Time: Unlike the natural history of SMA, which typically shows a decline of 1–2 HFMSE points annually, Itvisma stabilized or improved motor abilities through 52 weeks, independent of prior treatment history.
• Secondary Endpoints: While not all reached statistical significance due to multiplicity adjustments, trends favored Itvisma, including gains on the Revised Upper Limb Module and patient-reported outcomes.

These results were presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference and published in peer-reviewed outlets, confirming the therapy’s transformative potential.

STRENGTH Trial Insights

The open-label Phase IIIb STRENGTH study (n=approximately 30) focused on patients who had discontinued chronic therapies like nusinersen or risdiplam. It reinforced STEER’s findings, demonstrating motor stabilization and improvements in HFMSE scores over 52 weeks, with effects consistent across previously treated individuals. This trial highlighted Itvisma’s role as a potential “switch” therapy, addressing unmet needs in real-world scenarios