Phase III Trial Shows Novartis’ Gene Therapy Significantly Improves Spinal Muscular Atrophy Outcomes

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Results from the Phase III STEER and Phase IIIb STRENGTH trials show that Novartis’ investigational intrathecal gene therapy onasemnogene abeparvovec (OAV101 IT) significantly improved motor function in patients aged 2 to <18 years with spinal muscular atrophy (SMA). The trials show that patients administered OAV101 IT achieved a statistically significant improvement in Hammersmith Functional Motor Scale Expanded (HFMSE) scores compared to a sham control group, as well as motor function stabilization in patients who had discontinued Spinraza (nusinersen) or Evrysdi (risdiplam).¹

“In the STEER study evaluating treatment-naïve patients, OAV101 IT demonstrated a statistically significant improvement in motor function across a broad SMA population,” principal investigator Crystal Proud, MD, pediatric neurologist, Children's Hospital of the King's Daughters, said in a press release. “These results, paired with those in the STRENGTH study, support the potential for OAV101 IT to be a meaningful treatment option for people living with SMA with a goal of maintaining or improving motor function through a one-time therapy.”

The registrational STEER study evaluated the safety and efficacy of OAV101 IT in 126 patients aged 2 to <18 years who were able to sit but not stand, with 75 patients randomly assigned to receive OAV101 IT and 51 to receive a sham procedure. The primary endpoint of the study was change from baseline to 52 weeks in HFMSE score.

Results found that patients treated with OAV101 IT experienced a 2.39-point improvement in HFMSE score compared to 0.51 points in the sham control group. The most common adverse events (AEs) were upper respiratory tract infection and pyrexia. The most common serious AEs were pneumonia and vomiting in patients treated with OAV101 IT and pneumonia and lower respiratory tract infection for patients in the sham group.

The open-label STRENGTH study assessed the safety, tolerability, and efficacy of OAV101 IT in 27 patients with SMA who had previously discontinued nusinersen or risdiplam. Results found that the total HFMSE least squares total score was 1.05 from baseline to 52 weeks. All patients enrolled in the trial experienced at least one AE. The most common AEs included common cold, pyrexia, and vomiting.¹

According to the National Organization for Rare Disorders, approximately one in every 10,000 newborns are affected by SMA. It is equally common in males and females.; however, types I and II are more common in males.² According to Medscape, the carrier frequency is one in every 50 people.

There are four different classifications of SMA, with SMA type 1 most commonly occurring in patients between birth and six months of age. SMA type II most commonly occurs between six and 18 months of age, SMA type III usually occurs after 18 months of age, and onset of SMA type IV typically occurs in adulthood, with a mean onset age in the mid 30s. In patients with SMA type I, there is a 95% mortality rate by 18 months of age, with a median survival rate of seven months.³
“The data presented today from our OAV101 IT program reinforce our belief in this therapy, which has the potential to have a meaningful impact on a broad range of people with SMA through its continuous benefit via a one-time dose,” said Shreeram Aradhye, MD, president, development, chief medical officer, Novartis, in the press release. “Together with patients, caregivers and healthcare professionals, we are committed to continuing to advance our mission to lead innovation in SMA treatment and broaden therapy options with our gene replacement therapies.”

References

1. New Novartis Phase III data demonstrate meaningful efficacy and safety results of intrathecal onasemnogene abeparvovec in broad patient population with SMA. Novartis. March 19, 2025. Accessed March 20, 2025. https://www.novartis.com/news/media-releases/new-novartis-phase-iii-data-demonstrate-meaningful-efficacy-and-safety-results-intrathecal-onasemnogene-abeparvovec-broad-patient-population-sma

2. Spinal Muscular Atrophy. NORD. Accessed March 20, 2025. https://rarediseases.org/rare-diseases/spinal-muscular-atrophy/#disease-overview-main

3. Spinal Muscular Atrophy. Medscape. Accessed March 20, 2025. https://emedicine.medscape.com/article/1181436-overview#a6