Novartis’ Investigational Therapy for Spinal Muscular Atrophy Meets Primary Endpoint in Phase III Clinical Trial
Intrathecal onasemnogene abeparvovec (OAV101 IT) demonstrated an increase from baseline in Hammersmith Functional Motor Scale – Expanded total score in children and young adults with SMA.
Novartis has announced positive results from the Phase III STEER clinical trial of its investigational therapy, intrathecal onasemnogene abeparvovec (OAV101 IT) in treatment-naïve patients with spinal muscular atrophy (SMA) Type 2. The pivotal study met its primary endpoint with OAV101 IT demonstrating an increase from baseline in total Hammersmith Functional Motor Scale - Expanded (HFMSE) scores.1
Efficacy and safety results for the investigational therapy were compared against a sham control, a procedure designed to mimic the administration of OAV101 IT. The safety profile was favorable, with adverse events and serious adverse events being similar between arms.
In a press release, Shreeram Aradhye, MD, president, development and chief medical officer, Novartis, said, “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 two and above. 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.”
The STEER trial is a randomized, double-blind, sham-controlled study. The SMA Type 2 patient population is comprised of those aged two to less than 18 years who were able to sit, but had never walked independently. Over 100 patients were randomized to receive either OAV101 or the sham procedure over a 52-week period.
Results from the STEER trial are consistent with those of the Phase I/II open-label STRONG study, in which OAV101 IT treatment led to a clinically meaningful increase in HFMSE scores in one year and a clinically meaningful response in patients aged two to five years with SMA Type 2.
“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 the press 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.”
In March 2024, Novartis presented new data on the safety and efficacy of its approved gene therapy for SMA, Zolgensma (onasemnogene abeparvovec). The Phase IIIb open-label SMART trial evaluated Zolgensma in older and heavier children with SMA. According to the trial results, nearly all patients maintained or improved motor milestones after 52 weeks. These findings supplement a growing area of research in SMA.2
In an earlier press release, Sandra P. Reyna, MD, chief scientific advisor and head of global medical engagement for SMA at Novartis said, "This data—the first Zolgensma open-label clinical study to include older and heavier, as well as previously treated, patients—should build confidence among caregivers and healthcare professionals as they make informed treatment decisions, consistent with their local product label, for the studied patient population. We remain committed to reimagining possibilities for the SMA community.”
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 3, 2025. https://www.novartis.com/news/media-releases/novartis-intrathecal-onasemnogene-abeparvovec-phase-iii-study-meets-primary-endpoint-children-and-young-adults-sma
2. Novartis presents new data on safety and efficacy of Zolgensma, including maintained and improved motor milestones in older and heavier children with SMA. News release. Novartis. March 4, 2024. Accessed January 3, 2025. https://www.novartis.com/news/media-releases/novartis-presents-new-data-safety-and-efficacy-zolgensma-including-maintained-and-improved-motor-milestones-older-and-heavier-children-sma
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