Novartis has announced positive topline results from the Phase III STEER study, evaluating intrathecal onasemnogene abeparvovec (OAV101 IT) for the treatment of spinal muscular atrophy (SMA) Type 2. The study met its primary endpoint, demonstrating a statistically significant increase in motor function in treatment-naïve patients aged 2 to 18. This investigational gene therapy could broaden the treatment landscape for SMA, offering a new option for patients who have never walked independently.
The STEER trial (NCT05089656) was a randomized, double-blind, sham-controlled study involving over 100 patients with SMA Type 2. Participants were administered a one-time dose of OAV101 IT via intrathecal injection or a sham procedure. The primary endpoint was the change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score, a gold standard for assessing motor ability and disease progression in SMA. Secondary objectives included evaluating safety and efficacy using the Revised Upper Limb Module (RULM) scale.
Improved Motor Function with OAV101 IT
The STEER study demonstrated a clinically meaningful increase in HFMSE scores among patients treated with OAV101 IT compared to the sham control group. This improvement indicates better motor function in patients with SMA Type 2. Crystal Proud, M.D., Pediatric Neurologist and a Principal Investigator at Children's Hospital of the King's Daughters, noted that maintaining motor function is a key goal for older SMA patients, allowing them to continue daily activities more independently. "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."
Safety and Tolerability
The safety profile of OAV101 IT was favorable, with overall adverse events and serious adverse events being similar between the treatment and control arms. The most common adverse events were upper respiratory tract infection, pyrexia, and vomiting. These findings suggest that OAV101 IT is generally well-tolerated in this patient population.
Expanding Treatment Options for SMA
Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disease caused by a deficiency in the SMN1 gene, leading to the irreversible loss of motor neurons. This results in muscle weakness, atrophy, and impaired motor functions, including breathing, swallowing, and basic movement. The severity of SMA varies across a spectrum of types, with Type 2 characterized by onset between 6 and 18 months of age.
Currently, treatment options for SMA include chronic therapies such as nusinersen (Spinraza) and risdiplam (Evrysdi). Zolgensma (onasemnogene abeparvovec), an intravenous gene therapy, is approved for patients less than two years of age. OAV101 IT represents a potential one-time gene therapy option for older children with SMA Type 2, addressing an unmet need in this patient population.
Regulatory Plans and Future Directions
Novartis plans to share the STEER study results with regulatory agencies, including the US Food and Drug Administration (FDA), in 2025. If approved, OAV101 IT could broaden the patient population eligible for gene transfer therapy to include Type II SMA patients under 18 years of age. This would provide a valuable new treatment option, particularly in regions where newborn screening for SMA is not yet widely implemented, or where patients receive a delayed diagnosis.
Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis, stated, "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."
These results build upon the Phase I/II open-label STRONG study, which demonstrated clinically meaningful increases in HFMSE scores in one year following treatment with OAV101 IT. The STRENGTH study (NCT05386680) is an ongoing Phase 3b trial evaluating OAV101 IT in patients with SMA who have discontinued previous SMA therapies.
