Intrathecal gene therapy Itvisma effective in two Phase III trials in SMA

In SMN1-related proximal spinal muscular atrophy (SMA), the intravenous treatment Zolgensma is indicated for infants and young children weighing less than 21 kg with type I SMA or carrying a biallelic mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…). of the SMN1 gene and a maximum of 3 copies of the SMN2 gene. According to the Phase IIIAu cours d’un essai clinique de phase III, un médicament, pour lequel on a déterminé lors d’essais antérieurs l’innocuité et le dosage optimum (essais de phase I et II), est administré à un grand groupe de malades, sur une longue durée, dans le but d’évaluer son efficacité thérapeutique en la comparant à celle d’un traitement de référence ou un placebo. Il permet aussi de mettre en évidence les interactions indésirables et les effets secondaires du traitement à moyen terme. Au terme de cet essai, le médicament peut obtenir une autorisation de mise sur le marché. STEER and STRENGTH trials, the same gene therapy, this time administered intrathecally and called Itvisma, is effective in patients aged 2 to 18 years.

The multicentre STEER trial included 126 treatment-naïve patients aged 2 to 18 years who were able to sit but not walk independently.

• Seventy-five received gene therapy and 51 received a sham procedure.
• During one year of follow-up, motor function, the primary endpoint assessed using the HFMSE score, was significantly improved in treated patients compared to the control group.
• The greater improvement in the HFMSE score in the gene therapy group was observed as early as the fourth week of follow-up.
• This mode of administration was also well tolerated.

The STRENGTH multicentre trial involved 27 patients aged 2 to 18 years who had previously received treatment with Spinraza (nusinersen) or Evrysdi (risdiplam).

• All patients received Itvisma.
• The safety profile of gene therapy (primary endpoint) was consistent with that observed in treatment-naive patients.
• Motor function, assessed as a secondary endpoint using the HFMSE score, was stable during the one-year follow-up period.

Itvisma gene therapy has been approved in the United States for patients over 2 years of age since December, while in Europe, the application for approval is pending.

Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial. Kwon JM, Munell F, Le Goff L et al. Nat Med. 2025 Dec.

 

Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial. Proud CM, Chí Vũ D, Wilmshurst JM et al. Nat Med. 2025 Dec.