CHMP Backs Novartis' Intrathecal Onasemnogene Abeparvovec for 5q SMA in Older Patients

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Novartis’ gene therapy, intrathecal onasemnogene abeparvovec (Itvisma), for children aged 2 years and older, adolescents, and adults with 5q spinal muscular atrophy (SMA) and bi-allelic SMN1 mutations, according to the company.¹

If endorsed by the European Commission (EC), the therapy would extend gene-replacement treatment beyond the infant and young-child population currently associated with intravenous onasemnogene abeparvovec. Novartis said it expects a final decision from the EC in about 2 months.¹

“Living with SMA affects every stage of life, including education, employment, and independence,” Nicole Gusset, CEO of SMA Europe, said in a company press release.¹ “Older children, teenagers, and adults face fewer opportunities to benefit from innovative therapies. A positive CHMP opinion for Itvisma is an important step toward addressing this gap.”

How could intrathecal gene therapy expand treatment options for older patients with SMA?

The recommendation matters clinically because treatment options for older patients with SMA have largely centered on chronic splice-modifying therapies, whereas intrathecal onasemnogene abeparvovec is being positioned as a one-time gene-replacement approach. SMA is a rare neuromuscular disorder caused by loss of SMN1, leading to reduced survival motor neuron protein, progressive motor neuron degeneration, and worsening muscle weakness.²

The CHMP opinion was based primarily on a phase 3 trial (STEER), with supportive evidence from a phase 3b study (STRENGTH) and a phase 1/2 study (STRONG), Novartis said.^1,3,4

In the sham-controlled STEER study, 75 patients received intrathecal onasemnogene abeparvovec and 51 underwent a sham procedure. The company reported a 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE) in the active-treatment group versus 0.51 points in the sham group, for a statistically significant between-group difference (P = .0074).^1,3 Effects were reported as sustained through 52 weeks of follow-up.¹

What do the trial results suggest about efficacy and durability in later-stage SMA?

In the press release, Professor Tim Hagenacker of the Department of Neurology at University Hospital Essen in Germany stated that “even a 1-point difference in the HFMSE can translate into tangible functional gains for individuals with SMA, such as the ability to grasp a pen.”¹ That interpretation aligns with the practical importance of small motor changes in a progressive disorder, although the clinical meaning of a mean HFMSE difference should still be interpreted in the context of baseline disability, prior treatment exposure, and durability of response.

Published data from the STEER program in Nature Medicine support the company’s description of efficacy, although longer-term outcomes remain relevant for a gene therapy intended as a single-dose treatment.³ Supportive results from STRENGTH, also published in Nature Medicine, included both treatment-naive and previously treated patients, suggesting activity across a broader real-world population than is often represented in pivotal trials.⁴ The earlier STRONG phase 1/2 study, published in the Journal of Neuromuscular Diseases, provided initial evidence for intrathecal delivery of onasemnogene abeparvovec in older children with SMA.⁵

The treatment landscape for SMA has changed substantially in the past decade. For example, nusinersen and risdiplam increase SMN protein production through SMN2 modulation, and onasemnogene abeparvovec provides a functional copy of SMN1 through adeno-associated virus serotype 9 (AAV9)-mediated gene transfer.^6,7 Most gene therapy experience to date, however, has been in infants and younger children treated intravenously, in which earlier intervention is associated with better outcomes. Older children and adults with established disease may still benefit from stabilization or modest motor improvement, but expectations differ because motor neuron loss is not fully reversible.^2,7

References

1. Novartis. Novartis receives positive CHMP opinion for Itvisma for spinal muscular atrophy (SMA). Published April 24, 2026. Accessed April 24, 2026. https://www.novartis.com/news/media-releases/novartis-receives-positive-chmp-opinion-itvisma-spinal-muscular-atrophy-sma
2. Anderton RS, Mastaglia FL. Advances and challenges in developing a therapy for spinal muscular atrophy. Expert Rev. Neurother. 2015;15(8):895-908. doi: 10.1586/14737175.2015.1059757
3. Proud CM, Vũ DC, Wilmshurst JM, et al. Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial. Nat. Med. 2026;32(2):481-487. doi: 10.1038/s41591-025-04103-w
4. Kwon JM, Munell F, Le Goff L, et al. Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial. Nat. Med 2026;32:488–493. doi: 10.1038/s41591-025-04119-2
5. Finkel RS, Darras BT, Mendell JR, et al. Intrathecal Onasemnogene abeparvovec for sitting, nonambulatory patients with spinal muscular atrophy: Phase I ascending-dose study (STRONG). J Neuromuscul Dis. 2023;10(3):389-404. doi: 10.3233/JND-221560
6. Li Q. Nusinersen as a therapeutic agent for spinal muscular atrophy. Yonsei Med. J. 2020;61(4):273-283. doi: 10.3349/ymj.2020.61.4.273
7. Ratni H, Scalco RS, Stephan AH. Risdiplam, the first approved small molecule splicing modifier drug as a blueprint for future transformative medicines. ACS Med. Chem. Lett. 2021;12(6):874-877. doi: 10.1021/acsmedchemlett.0c00659