Novartis Advances Intrathecal Zolgensma for Older SMA Patients, Showing Promise in Late-Stage Trials

Novartis has unveiled promising results from two late-stage clinical trials of an intrathecal formulation of its gene therapy Zolgensma, designed to treat older patients with spinal muscular atrophy (SMA). The data, presented at the Muscular Dystrophy Association's Clinical & Scientific Conference in Dallas, demonstrate the potential for this new formulation to expand treatment options for SMA patients beyond the current age and weight restrictions of the intravenous version.

STEER and STRENGTH Trials Showcase Efficacy and Safety

The Phase III STEER trial, which enrolled treatment-naïve SMA patients aged 2 to 18 years, showed that intrathecal Zolgensma (OAV101 IT) led to a 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE) after one year of treatment. This improvement was statistically significant compared to the 0.51-point improvement observed in the sham control group.

In the Phase IIIb STRENGTH trial, which focused on patients who had previously discontinued treatment with Biogen's Spinraza or Roche's Evrysdi, OAV101 IT demonstrated the ability to stabilize motor function over 52 weeks. The safety profile in both trials was consistent, with adverse events similar between treatment and placebo groups.

Norman Putzki, Novartis' global development head of neuroscience and gene therapy, emphasized the significance of these results, stating, "You see there's a prevention of further progression of the disease, further decline, losing these motor abilities that patients need in order to take care of themselves."

Expanding Treatment Options for Older SMA Patients

The intrathecal formulation of Zolgensma addresses a critical need in the SMA community by potentially offering a one-time gene therapy option for patients over two years of age. The current intravenous version of Zolgensma is limited to children under two years old in the U.S. or patients weighing up to 21 kilograms in Europe due to safety concerns with higher doses required for older, heavier patients.

Crystal Proud, M.D., a principal investigator at the Children's Hospital of the King's Daughters, commented on the potential impact of OAV101 IT, saying it could be "a meaningful treatment option for people living with SMA with a goal of maintaining or improving motor function through a one-time therapy."

Looking Ahead: Regulatory Filings and Market Potential

Based on the positive results from the STEER and STRENGTH trials, Novartis plans to file for regulatory approval of OAV101 IT in the first half of 2025. If approved, it would become the first gene replacement therapy for SMA patients over two years of age, potentially addressing a significant unmet need in the treatment landscape.

Novartis estimates that intrathecal Zolgensma could become a multibillion-dollar product at peak, underscoring the potential market impact of this new formulation. As the SMA treatment paradigm continues to evolve rapidly, the introduction of OAV101 IT could mark another significant milestone in the ongoing efforts to improve outcomes for patients living with this rare neuromuscular disease.