New Phase 3 Data for AAV Gene Therapy OAV101 IT Shows Motor Improvement in Older Children and Teens with SMA

December 8, 2025 — New research published today in Nature Medicine reveals that a single dose of the AAV (adeno-associated virus) gene replacement therapy, onasemnogene abeparvovec, delivered intrathecally (OAV101 IT), significantly improved motor function in children over 2 years of age and adolescents with spinal muscular atrophy (SMA).

The AAV gene therapy, known commercially as Zolgensma (onasemnogene abeparvovec), is an AAV9 vector that delivers the SMN (survival motor neuron) transgene. The therapy, previously approved only for infants, now shows potential to address the unmet need in older patients.

Expanding Access with Intrathecal AAV Delivery

Spinal muscular atrophy (SMA) is a rare genetic condition caused by the inability to produce enough survival motor neuron (SMN) protein, leading to progressive muscle weakness and loss of movement.

OAV101 IT (onasemnogene abeparvovec delivered intrathecally) is an AAV gene therapy designed to restore the production of this missing SMN protein in a single treatment. The therapy utilizes an AAV9 vector to deliver the functional SMN transgene. The current intravenous AAV therapy is approved only for infants under two.

To address the need in older patients, Richard Finkel and colleagues assessed the safety and efficacy of a single dose of the AAV9 vector delivered directly into the spinal fluid (intrathecally) in patients aged 2 to 18 years.

Significant Motor Function Gains in Clinical Trial

The year-long Phase 3 trial randomized 126 participants—all capable of sitting but unable to walk independently—to receive either the AAV gene therapy (OAV101 IT) (75 participants) or a placebo (51 participants).

• Primary Finding: Participants who received the AAV gene therapy achieved a significantly greater improvement in motor function scores compared to the placebo group.

• Mechanism: The AAV9 vector successfully delivered the SMN transgene via the intrathecal route, leading to measurable gains in 33 specific motor skills, such as moving from lying to sitting, walking, and climbing stairs.

Side effects were similar across both groups and were generally manageable. These results strongly support broadening access to this AAV gene therapy for SMA to older children and adolescents. However, the study’s 12-month duration necessitates longer-term monitoring to confirm the long-term safety and efficacy of the AAV treatment.