Novartis Advances New SMA Gene Therapy with Promising Late-Stage Data

Novartis, the Swiss pharmaceutical giant, has unveiled detailed results from its STEER study, bolstering the case for OAV101, a potential successor to its blockbuster spinal muscular atrophy (SMA) gene therapy, Zolgensma. The company aims to expand treatment options for a broader range of SMA patients, including those previously ineligible for Zolgensma.

STEER Study Results Support Broad Application

The STEER trial, a pivotal late-stage study, evaluated OAV101 in children with moderate SMA aged two years and older who had not received prior targeted therapies. Key findings include:

• OAV101-treated patients showed a 2.39-point improvement on the motor function scale, compared to a 0.51-point gain in the sham group.
• All secondary endpoints consistently favored OAV101, though statistical significance was not achieved.
• Safety profile was comparable between treatment and control groups, with upper respiratory tract infection and fever being the most common adverse events.

Novartis emphasized the infrequent occurrence of liver enzyme elevations, a crucial safety consideration for gene therapies. No cases of Hy's law, an indicator of severe liver damage risk, were reported.

Expanding Treatment Horizons

OAV101 shares the same active ingredient as Zolgensma but is administered intrathecally, directly into the spine. This approach aims to overcome the age and weight limitations of Zolgensma, which is only approved for patients under two years old and is administered intravenously.

The STRENGTH trial, an open-label study involving 27 participants who had previously discontinued treatment with competing therapies Spinraza or Evrysdi, provided additional supportive data. Results indicated that OAV101 could stabilize motor function in these patients, though all participants experienced at least one adverse event.

Strategic Implications and Market Potential

Novartis CEO Vas Narasimhan has expressed high expectations for OAV101, projecting annual sales of $3 billion. The company plans to submit an approval application by the end of June, anticipating a launch trajectory similar to Zolgensma's rapid initial uptake.

Dr. Crystal Proud, a pediatric neurologist involved in the trials, noted that the combined results from STRENGTH and STEER suggest OAV101 could be a "meaningful treatment option" for SMA patients.

As Novartis prepares for potential market entry, the company emphasizes OAV101's one-time dosing regimen and established efficacy measures as key differentiators in the evolving SMA treatment landscape.