Zolgensma: STEER Trial Achieves Key Milestones in SMA Treatment

Novartis Zolgensma (onasemnogene abeparvovec) has reached a significant milestone in the treatment of spinal muscular atrophy (SMA) with the Phase 3 STEER trial demonstrating positive results. The trial, which focused on intrathecal (IT) administration for older patients with SMA type 2, successfully met its primary endpoint and could lead to broader FDA approval and patient accessibility.

Mechanism of Action

Zolgensma is designed to replace the missing or defective SMN1 gene in SMA patients. It uses a non-replicating AAV9 vector to deliver the functional gene directly to motor neurons, restoring the production of survival motor neuron (SMN) protein. This protein is crucial for the health and function of motor neurons, which control muscle movement. By increasing SMN protein levels, Zolgensma aims to halt the progression of SMA and improve motor function.

Formulation and Trial Design

The STEER trial (NCT05089656) introduced an IT formulation of Zolgensma (OAV101 IT). This method involves administering gene therapy directly into the spinal canal, ensuring more targeted delivery to motor neurons. This approach contrasts with the standard intravenous (IV) infusion used in younger patients, providing a tailored solution for those with advanced disease progression.

The study enrolled over 100 children with SMA type 2, ages 2-17, who were able to sit independently but had not walked unaided. Participants were randomly assigned to receive either OAV101 IT or a sham procedure. After one year, those in the sham group could receive OAV101 IT, while the treatment group received a sham procedure and was monitored for three additional months. The main goal was to assess changes in motor function using the HFMSE score.

Key Findings

Primary Endpoint Achieved: Results showed that patients treated with IT Zolgensma had significant improvements in their HFMSE scores compared to the sham group. The trial met its primary endpoint, demonstrating significant improvements in motor function, particularly through enhanced upper limb function.

Safety Profile: IT Zolgensma was well-tolerated, with adverse effects being manageable, underscoring its safety for older SMA patients.

Zolgensma was approved by the U.S. FDA in 2019 for children with SMA under 2 years old?and is given through an IV infusion. The success of the STEER trial paves the way for expanding Zolgensma’s use beyond infants. Older patients, especially those with SMA type 2, could greatly benefit from this targeted gene therapy. Novartis plans to share results with regulatory agencies this year to make the treatment available for SMA patients in need. Broader FDA approval could provide new hope and enhanced quality of life for a larger group of SMA patients, solidifying Zolgensma’s role as a critical therapy in managing the disease.

Source: Novartis PR Link.