Novartis Secures EU Approval for Itvisma® in SMA
Novartis has announced that the European Commission (EC) has granted approval for Itvisma® (onasemnogene abeparvovec) for the treatment of children aged two years and older, adolescents, and adults living with 5q spinal muscular atrophy (SMA) who have a bi-allelic mutation in the survival motor neuron 1 (SMN1) gene. The approval marks a significant milestone in the treatment of spinal muscular atrophy by expanding access to gene replacement therapy beyond infants and very young children to include a much broader patient population across the European Union.
With this decision, Itvisma becomes the first and currently the only gene replacement therapy approved in the European Union for older children, teenagers, and adults with 5q SMA. The approval provides healthcare professionals with a new therapeutic option designed to address the genetic cause of the disease through a one-time treatment rather than requiring ongoing administration throughout a patient’s lifetime.
The European Commission’s decision follows a review of clinical evidence demonstrating improvements in motor function among treated patients and reflects continued progress in the evolution of gene therapies for rare neuromuscular diseases. For many individuals living with spinal muscular atrophy, the approval represents an important expansion of available treatment options and offers the possibility of receiving a therapy specifically designed to replace the missing or defective gene responsible for the disease.
Expanding Treatment Options for a Broader SMA Population
Spinal muscular atrophy is a rare, inherited neuromuscular disorder characterized by progressive degeneration of motor neurons located within the spinal cord. As these specialized nerve cells deteriorate, communication between the brain and skeletal muscles becomes increasingly impaired, leading to progressive muscle weakness, loss of motor function, and, in severe cases, life-threatening complications affecting breathing and swallowing.
The disease is caused primarily by mutations or deletions in the survival motor neuron 1 (SMN1) gene. The absence of a functional SMN1 gene leads to insufficient production of survival motor neuron protein, which is essential for maintaining the health and function of motor neurons.
Without adequate levels of this protein, motor neurons gradually degenerate, resulting in progressive muscle wasting and declining physical function.
Although spinal muscular atrophy has traditionally been classified into different clinical types based on age of onset and maximum motor function achieved, advances in newborn screening and disease-modifying therapies have significantly changed the clinical landscape over the past decade.
However, many older children, adolescents, and adults living with SMA have historically had more limited access to gene replacement therapies specifically approved for their age group.
The approval of Itvisma addresses this important treatment gap by extending gene replacement therapy to a broader spectrum of patients.
A One-Time Gene Replacement Therapy
Unlike therapies that require repeated administration throughout a patient’s life, Itvisma has been developed as a one-time gene replacement treatment.
The therapy utilizes a viral vector to deliver a functional copy of the SMN1 gene into patients’ cells. Once delivered, the replacement gene is intended to enable production of the survival motor neuron protein that is deficient in individuals with SMA.
By directly addressing the underlying genetic cause of the disease, Itvisma seeks to restore production of the essential protein required for motor neuron function rather than simply modifying downstream biological pathways.
Another distinguishing feature of Itvisma is its fixed-dose administration.
According to Novartis, the treatment is delivered as a single fixed dose that does not require adjustment based on a patient’s age or body weight.
This simplified dosing strategy differs from certain other therapies that require ongoing treatment schedules and dose modifications throughout a patient’s life.
The availability of a one-time therapeutic option provides physicians and patients with an additional treatment approach that may better align with individual medical needs and personal preferences.
Addressing the Genetic Root Cause of Disease
The scientific principle underlying Itvisma centers on correcting the fundamental genetic deficiency responsible for spinal muscular atrophy.
Most individuals with 5q SMA possess bi-allelic mutations in the SMN1 gene, meaning both inherited copies of the gene are nonfunctional.
As a result, production of survival motor neuron protein falls below the level necessary to maintain healthy motor neuron function.
Although patients also possess one or more copies of a related gene, SMN2, the protein produced by this backup gene is insufficient to fully compensate for the missing SMN1 function.
Gene replacement therapy seeks to overcome this limitation by introducing a functional SMN1 gene capable of restoring production of full-length survival motor neuron protein.
Improved protein expression may help preserve motor neurons, slow disease progression, and support improvements in motor function.
Because Itvisma directly targets the underlying genetic defect, it represents a fundamentally different therapeutic strategy from treatments that modify SMN2 gene splicing or require repeated administration over time.
Importance of Maintaining Motor Function
Motor function remains one of the most important clinical outcomes for individuals living with spinal muscular atrophy.
Many patients experience gradual declines in strength, mobility, balance, and independence over time as motor neuron degeneration progresses.
Maintaining existing motor abilities—or achieving even modest improvements—can significantly affect daily living, allowing patients to perform activities independently for longer periods and improving overall quality of life.
For older children, adolescents, and adults, preserving upper limb function, walking ability, sitting balance, or respiratory muscle strength may have meaningful impacts on education, employment, social participation, and long-term health.
The Novartis availability of an additional therapeutic option designed specifically for these patient populations therefore represents an important advancement in clinical care.
Approval Supported by Multiple Clinical Studies
The European Commission based its approval on evidence generated from several clinical studies evaluating the safety and effectiveness of Itvisma across multiple patient populations.
The primary evidence supporting regulatory approval came from the registrational STEER study, supplemented by findings from the Phase IIIb STRENGTH study and the earlier Phase I/II STRONG clinical trial.
Together, Novartis these studies provided a comprehensive evaluation of the therapy’s clinical performance in individuals living with spinal muscular atrophy.
The inclusion of multiple studies allowed regulators to assess treatment effects across different patient groups while evaluating both safety and improvements in motor function.
Results from the STEER Trial
The pivotal STEER study served as the principal registrational trial supporting the European approval.
According to Novartis, patients treated with Itvisma achieved a statistically significant improvement of 2.39 points on the Hammersmith Functional Motor Scale Expanded (HFMSE), an established clinical assessment used to measure motor function in individuals with spinal muscular atrophy.
The HFMSE evaluates a range of physical abilities including sitting, standing, rolling, crawling, and walking depending on each patient’s baseline functional status.
Improvements on this scale may indicate better motor performance or slower disease progression.
Importantly, the Novartis treatment benefits observed during the STEER trial were sustained throughout 52 weeks of follow-up, suggesting continued functional improvements over the one-year observation period.
Additional Evidence from STRENGTH and STRONG
The approval was further supported by data generated in the STRENGTH and STRONG clinical studies.
These studies evaluated Itvisma in both treatment-naïve patients and individuals who had previously received other SMA therapies.
Results demonstrated clinically meaningful benefits across these patient groups, providing additional evidence that gene replacement therapy may offer advantages regardless of prior treatment history.
The Novartis availability of supportive data from multiple clinical trials strengthens confidence regarding the therapy’s overall clinical profile while expanding understanding of its potential role within the broader SMA treatment landscape.
Patient Advocacy Community Welcomes Approval
Nicole Gusset, Chief Executive Officer of SMA Europe, described the European Commission’s decision as an important milestone for individuals and families affected by spinal muscular atrophy.
She emphasized that beyond its scientific significance, the approval brings the possibility of an additional treatment option closer to patients seeking therapies that align with their individual medical circumstances and personal treatment preferences.
According to Gusset, Novartis the availability of multiple therapeutic choices is increasingly important as clinicians tailor treatment decisions based on each patient’s disease stage, previous therapy, functional status, and long-term goals.
She also expressed hope that regulatory approval will translate into timely and equitable patient access throughout European healthcare systems, ensuring that eligible individuals can benefit from the newly approved therapy without unnecessary delays.
Clinical Experts Highlight Expanded Treatment Choices
Professor Jana Haberlová, Head of the Neuromuscular Centre within the Department of Paediatric Neurology at Motol and Homolka University Hospital in Prague, highlighted the importance of maintaining or improving motor function for older individuals living with spinal muscular atrophy.
She explained that preserving physical function can have substantial impacts on daily activities and overall quality of life for children, adolescents, and adults affected by the disease.
According to Professor Haberlová, Novartis the European approval of Itvisma expands available treatment options by introducing gene replacement therapy to a broader patient population than previously served.
The Novartis approval also provides clinicians with another therapeutic approach that can be incorporated into individualized treatment planning throughout the course of the disease.
Novartis Expands Its SMA Gene Therapy Portfolio
Patrick Horber, MD, President of International at Novartis, described the approval as a major milestone for the global spinal muscular atrophy community.
He noted that Itvisma enables Novartis to extend access to one-time gene replacement therapy beyond infants and young children, addressing longstanding unmet needs among older patients who previously had fewer gene therapy options.
Horber also pointed out that the approval complements Novartis’ existing SMA portfolio.
Together with Zolgensma, the Novartis company can now offer gene replacement therapies spanning different stages of spinal muscular atrophy across Europe, ranging from newborn infants identified through early diagnosis to adults living with later-stage disease.
This broader therapeutic portfolio allows physicians greater flexibility when selecting treatment strategies based on patient age, disease progression, and clinical circumstances.
A New Era for Gene Therapy in Spinal Muscular Atrophy
The Novartis European Commission’s approval of Itvisma reflects continued progress in applying gene replacement technologies to inherited neurological diseases. As understanding of spinal muscular atrophy has advanced, treatment has evolved from supportive care alone to targeted molecular therapies capable of modifying the disease process.
The availability of a one-time gene replacement therapy for children aged two years and older, adolescents, and adults significantly expands therapeutic options for patients living with 5q spinal muscular atrophy throughout the European Union. By directly replacing the defective SMN1 gene responsible for the disease, Itvisma offers an innovative approach designed to address the genetic root cause of SMA while supporting improvements in motor function.
With clinical evidence demonstrating sustained functional benefits and regulatory approval now secured, Novartis is positioned to broaden access to gene replacement therapy across a larger segment of the SMA community. As Novartis healthcare systems begin implementing the approval across Europe, eligible patients and their families may soon gain access to a new treatment option that has the potential to reshape long-term management of one of the most challenging inherited neuromuscular disorders.
About SMA
Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disease caused by a mutated or missing SMN1 gene.4,5 The SMN1 gene is responsible for producing most of the SMN protein a body needs for muscle function, including breathing, swallowing and basic movement.5 Without it, motor neurons are irreversibly lost, leading to progressive, debilitating muscle weakness.5
A second gene, the SMN2 gene, produces a small fraction (~10%) of functional SMN protein compared with the SMN1 gene.6 Novartis Individuals with more copies of the SMN2 gene generally have a less severe form of SMA than those with fewer copies.6 SMA has an estimated global prevalence of around 1 to 2 per 100,000 people, with an incidence of roughly 1 in 10,000 live births.7
About Itvisma® (onasemnogene abeparvovec)
Itvisma, an adeno-associated virus 9 (AAV9)-based gene therapy, is uniquely 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 SMN protein expression with a single, one-time intrathecal injection. The most common side effects with Itvisma include upper respiratory tract infection, pyrexia, vomiting, headache and increased hepatic enzymes.1,2,3 Results from the STEER and STRENGTH studies were published in Nature Medicine.1,2
Novartis has an exclusive, worldwide license with Nationwide Children’s Hospital to both the intravenous and intrathecal delivery of AAV9 gene replacement therapy for the treatment of all types of SMA; an exclusive, worldwide license from REGENXBIO for any recombinant AAV vector in its intellectual property portfolio for the in vivo gene replacement therapy treatment of SMA in humans; an exclusive, worldwide licensing agreement with Généthon for in vivo delivery of AAV9 vector into the central nervous system for the treatment of SMA.