Phase 3 STEER Study of SMA Gene Therapy Meets Primary End Point

The phase 3 STEER study (NCT05089656) of intrathecal onasemnogene abeparvovec (OAV101 IT; Novartis) met its primary end point, showing increased total Hammersmith Functional Motor Scale - Expanded (HFMSE) scores among patients with spinal muscular atrophy (SMA) type 2.¹ Data from the study will be presented at a medical meeting in 2025, according to a press release from Novartis.

Type 2 SMA is characterized by decreased muscle tone and weakness manifesting between 6 and 18 months of age.² These patients may sit up, but cannot walk, and approximately 70% of patients with type 2 SMA live to the age of 25 years. SMA is caused by mutations in the SMN1 gene, and the cause of death for patients with SMA is typically respiratory issues. Intrathecal onasemnogene abeparvovec is an investigational SMA gene therapy that has been evaluated in the phase 1/2 STRONG study (NCT03381729), the phase 3B STRENGTH study (NCT05386680), and the STEER study. It is a one-time treatment aiming to preserve motor function in patients with SMA.¹

“Maintaining motor function is a key goal for many older patients with SMA. This may allow them the capacity to continue to propel their electric wheelchair, feed themselves with intact hand to mouth function, and perform other activities of daily living as independently as possible,” Crystal Proud, MD, pediatric neurologist and a principal investigator at Children's Hospital of the King's Daughters, said in a Novartis news release. “OAV101 IT administration has not only been demonstrated to maintain motor function, but also increased it in indicating the impact a one-time therapy could have.”

Intrathecal onasemnogene abeparvovec is an investigational SMA gene therapy that has been evaluated in the phase 1/2 STRONG study, the phase 3B STRENGTH study, and the STEER study. | Image credit: wladimir1804 - stock.adobe.com

The pivotal STEER study assessed the safety and efficacy of intrathecal onasemnogene abeparvovec in patients aged 2 to less than 18 years with previously untreated SMA type 2. Patients were able to sit but had never walked unassisted. The study utilized a sham control, which mimicked gene therapy administration without delivering treatment. The main end point was HFMSE scores, with secondary end points assessing safety and efficacy using the Revised Upper Limb Module scale. The HFMSE is a validated test designed to assess motor abilities and disease progression in SMA.

In the study, more than 100 patients were randomized to receive either intrathecal onasemnogene abeparvovec or the sham procedure, and there was an increase in HFMSE scores among those who received the gene therapy vs the sham control group. This finding shows improved motor function in patients given onasemnogene abeparvovec. The safety profile was also favorable, with similar adverse events between the groups. Upper respiratory tract infections, pyrexia, and vomiting were the most common adverse events in the study.

These results build on those seen in the STRONG trial, which was an open-label dose ranging study and showed a clinically meaningful increase in HFMSE scores in 1 year.

“Many patients with SMA currently rely on chronic treatments to manage their disease. These positive topline results from the STEER trial underscore the efficacy, safety and tolerability of OAV101 IT in patients with SMA aged 2 and above,” Shreeram Aradhye, MD, president of development and chief medical officer at Novartis, said in the release. “The totality of evidence clearly supports a positive risk benefit profile of OAV101, which is expected to support registration covering a broad range of SMA patients. We remain committed to leading innovation in SMA treatment through our one-time gene therapies, uniquely designed to replace the function of the missing or defective SMN1 gene.”

References

1. Novartis intrathecal onasemnogene abeparvovec phase III study meets primary endpoint in children and young adults with SMA. News release. Novartis. December 30, 2024. Accessed January 14, 2025. https://www.novartis.com/news/media-releases/novartis-intrathecal-onasemnogene-abeparvovec-phase-iii-study-meets-primary-endpoint-children-and-young-adults-sma

2.Spinal muscular atrophy (SMA). Cleveland Clinic. Updated June 6, 2024. Accessed January 14, 2025. https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma