MDA 2026: Itvisma, Zolgensma show extended safety, efficacy in SMA
Gene replacement therapies offer the potential for lasting benefit
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Itvisma, a gene therapy for SMA, showed continued motor function improvements and sustained safety.
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Zolgensma, for SMA infants, demonstrated long-term motor gains in real-world data.
- The results support the safety and efficacy of gene therapy in several SMA groups.
The motor function benefits of Itvisma (onasemnogene abeparvovec-brve), one of two Novartis’ gene therapies for spinal muscular atrophy (SMA), continued to increase over more than one year of treatment, extended Phase 3 trial results show.
These findings come from the STEER Phase 3 trial (NCT05089656), which supported the U.S. Food and Drug Administration’s approval of Itvisma last year.
“The SMA community has largely viewed this approval as a meaningful and long-awaited milestone, particularly for children over the age of 2, teens and adults, who previously had limited access to one-time treatment options,“ Nazem Atassi, MD, senior vice president and global development head of neurology and gene therapy at Novartis, said in a written interview with SMA News Today.
The latest results from STEER were presented in a poster at the 2026 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, which took place last week in Orlando, Florida. The poster was titled “Intrathecal Onasemnogene Abeparvovec (OAV101) for Patients with Spinal Muscular Atrophy (SMA): Extended 64-Week Outcomes from the Phase 3 STEER Study.” Several co-authors are employees of Novartis.
Itvisma group continued to experience motor improvements
Mutations in the SMN1 gene are the chief cause of SMA, resulting in a deficiency of the survival motor neuron (SMN) protein. SMN helps support the specialized nerve cells that control movement, called motor neurons. Without enough working SMN, the nerve cells sicken and die, leading to SMA symptoms, including muscle weakness and wasting.
Like Zolgensma (onasemnogene abeparvovec-xioi), the first approved SMA gene therapy that can be used to treat newborns and toddlers younger than 2, Itvisma delivers a working version of SMN1 packaged into a viral carrier, which cells can then use to produce SMN. Whereas Itvisma is given via an injection into the spinal canal, Zolgensma is given by intravenous (into-the-vein) infusion.
STEER investigated the safety and efficacy of Itvisma for participants ages 2 to 17. Initially, 75 participants received Itvisma and 51 received a sham procedure designed to mimic the Itvisma administration but without any active treatment. One year after the injection, the Itvisma group showed a statistically significant and clinically meaningful improvement in motor function, measured with the Hammersmith Functional Motor Scale-Expanded (HFMSE), compared with the sham group.
Data shown at the MDA Conference spanned nearly three more months, for a total of 64 weeks. At the one-year mark, participants in the Itvisma group received a sham procedure, whereas those initially assigned to the sham procedure group were given the gene therapy. Most participants from the yearlong part of the study continued into its additional 12 weeks.
Patient safety is our top priority.
During that second period, the group that had received Itvisma during part one continued to experience motor improvements. The average HFMSE improvement was about 2.41 points after part one, increasing to 2.75 points after part two. Similar improvements were found in another standard motor function scale that assesses arm and hand function, the Revised Upper Limb Module.
These improvements could translate to meaningful change for participants, according to Atassi.
“Depending on the person, this level of score increase could potentially mean improved ability to reach, lift, feed themselves, operate a device, or perform other routine activities with less assistance,” he said.
No new safety concerns arose during the additional three months of study. The most common side effects included upper respiratory tract infections, fever, and vomiting.
“Patient safety is our top priority. Gene replacement therapy is a highly innovative approach that offers the potential for lasting benefit,” Atassi said. “Like all approved treatments, it undergoes rigorous evaluation in clinical trials to assess safety and efficacy, and patients are closely monitored during and after treatment.”
Zolengsma results underscore benefits of newborn screening
In a separate poster, “Long-Term Real-World Outcomes Following Onasemnogene Abeparvovec Monotherapy for Patients with SMA: Updated Findings from the RESTORE Registry,” a team including investigators at Novartis presented an analysis of the ongoing real-world RESTORE registry.
The analysis included 257 participants with various types of SMA who received treatment with Zolgensma at a median age of 3 months. Most patients were treated in the U.S. and were diagnosed via newborn screening. RESTORE, an observational study, has a follow-up duration of up to 15 years.
Results showed improvements in several metrics of motor function, including the HFMSE and the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND). Among participants with CHOP-INTEND data, about three-quarters experienced an increase of at least four points at the last visit, which occurred at about 3.5 years post-treatment. Additionally, nearly 90% met or maintained a score of at least 40 points.
“Generally, it is unusual for infants with SMA to achieve a 40+ CHOP-INTEND motor function without treatment,” Atassi said. “Maintaining or achieving CHOP-INTEND scores at that level may indicate preservation or improvement of abilities such as head control, movement against gravity, and other foundational motor skills that are important for development.”
Some participants had up to five years of follow-up data showing sustained improvements in motor abilities. The analysis further showed that children diagnosed with newborn screening were younger when they reached the first motor milestone — such as head control, turning side to side, or standing with assistance — relative to clinically diagnosed patients.
“This … outcome contrasts [with] the natural progression of this disease that limits basic movement in children, including the ability to breathe or swallow, underscoring the tangible benefits of newborn screening and early intervention with gene therapy,” Atassi said.
“Consistently younger age of motor milestone achievement for patients diagnosed by [newborn screening] further supports the benefit of early diagnosis and treatment,” the scientists wrte.
Regarding safety, Atassi added that the side effects of Zolgensma are “monitorable and manageable.” Lab monitoring before and after treatment can help identify potentially serious side effects, including effects on liver function, Atassi noted.
Although seven deaths occurred during the observation period, none were considered related to the gene therapy. No new safety signals were detected.
“For Zolgensma, the long-term and real-world data continue to reinforce the meaningful impact a one-time gene therapy can have for eligible children, including the potential for durable motor gains and outcomes that differ from the natural history of SMA,” Atassi added.
Together, the results from STEER and RESTORE support the safety and efficacy of gene therapy in several SMA groups.
“We remain committed to continuing to study these therapies, monitor safety closely, and work with healthcare providers, families, and the broader SMA community to help bring forward meaningful treatment options,” Atassi concluded.
Note: The SMA News Today team is providing live coverage of the 2026 MDA Clinical & Scientific Conference March 8-11 in Orlando, Florida. Go here to see the latest stories from the conference.
