Novartis' Intrathecal Onasemnogene Abeparvovec Phase III Study Meets Primary Endpoint

Novartis announced today that its Phase III study of intrathecal onasemnogene abeparvovec (brand name: Zolgensma) has successfully met its primary endpoint, showing significant clinical improvements in children and young adults with spinal muscular atrophy (SMA). The data from this global trial marks a promising step forward in the treatment of SMA, a rare, genetic neurodegenerative disease that leads to muscle weakness and, in severe cases, early death.

The trial evaluated the efficacy and safety of onasemnogene abeparvovec delivered via intrathecal (directly into the spinal fluid) injection, a delivery method designed to target the central nervous system more effectively. The primary endpoint of the study was the improvement in motor function, as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE), a widely used assessment for SMA. The results showed statistically significant improvements in motor function for children and young adults treated with the therapy compared to baseline measures.

SMA, caused by mutations in the SMN1 gene, leads to a progressive loss of motor neurons, significantly impairing muscle strength and movement. Prior to the approval of Zolgensma in its current form (IV administration), treatment options were limited, and the disease often led to irreversible damage and early death, particularly in the most severe cases, such as SMA Type 1.

This intrathecal formulation of onasemnogene abeparvovec is designed to address the needs of older patients who may not have been eligible for intravenous treatment. By offering a new, potentially more effective delivery method for the therapy, Novartis aims to broaden the impact of Zolgensma, especially in those with later-onset forms of SMA who still experience significant functional decline.

"This milestone represents a significant advancement in SMA care and brings hope to patients who have been previously underserved by available treatments," said Nimisha Nair, Global Head of Neurosciences at Novartis. "We are excited by the potential of intrathecal Zolgensma to offer a meaningful treatment option for a broader range of children and young adults with SMA."

The study also assessed the safety profile of the intrathecal formulation. According to Novartis, the treatment was generally well-tolerated, with no new safety concerns identified compared to the previously approved intravenous formulation.

The company is now preparing to submit these findings to regulatory authorities worldwide, with the hope of expanding the approved indications for onasemnogene abeparvovec to include intrathecal administration. If approved, this new method of delivery could provide a significant therapeutic option for SMA patients, potentially improving quality of life and delaying disease progression.

About Onasemnogene Abeparvovec (Zolgensma)

Zolgensma is a gene therapy that works by replacing the missing or nonfunctional SMN1 gene with a fully functional copy, aiming to address the underlying cause of SMA. It was initially approved by the U.S. FDA in 2019 for use in children under 2 years of age and has since been shown to improve motor function in infants with SMA. The new intrathecal formulation expands its potential use to a broader age range.

The results from this Phase III study come as a beacon of hope for the SMA community, where early intervention remains crucial. With SMA affecting approximately 1 in 10,000 live births globally, the treatment landscape has evolved rapidly, and Novartis is positioning Zolgensma as a cornerstone of therapy for the disease.