SMA: gene therapy effective via intrathecal administration in patients aged 2 to 18 years
While gene therapy is currently administered intravenously in infants with spinal muscular atrophy (SMA), two recent clinical trials show that it is also effective when delivered intrathecally in older patients.
In 5q spinal muscular atrophy linked to SMN1 (SMA), the treatment Zolgensma is indicated in infants and young children weighing less than 21 kg, notably those with type I SMA. This one-time intravenous gene therapy delivers the SMN1 gene using a viral vector.
Two recent studies showed that this gene therapy is also effective in patients aged 2 to 18 years when administered intrathecally, meaning directly into the cerebrospinal fluid in the lower back, similarly to a lumbar puncture. Under this formulation, the therapy is called Itvisma.
A therapy already approved in the United States
The STEER trial included 126 patients aged 2 to 18 years with SMA who had not previously received another innovative treatment and who were able to sit independently but not walk independently. Seventy-five received Itvisma and 51 underwent a “sham” procedure (control group).
Over one year of follow-up, motor function significantly improved in patients who received gene therapy compared with the control group, with differences observed as early as four weeks after treatment.
In practice, many patients may already have been treated with Spinraza (nusinersen) or Evrysdi (risdiplam), the two other innovative therapies currently available for SMA. For this reason, the STRENGTH trial evaluated the efficacy of intrathecal gene therapy in 27 patients aged 2 to 18 years previously treated with one of these two therapies. Unlike the STEER trial, all patients in this study received gene therapy.
After one year, stabilisation of motor function was observed, and treatment tolerability was consistent with that reported in patients treated with Itvisma who had not previously received another innovative therapy.
Based on the results of these two studies, the U.S. Food and Drug Administration (FDA) authorised intrathecal gene therapy Itvisma in November for patients with SMA older than 2 years. Marketing authorisation is currently under review in Europe.
Sources
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.