Novartis has released positive topline results from the phase 3 STEER trial evaluating OAV101 IT (intrathecal onasemnogene abeparvovec) in treatment-naïve patients with spinal muscular atrophy (SMA) Type 2, aged two to under 18 years.
The STEER trial is a pivotal, sham-controlled study designed to evaluate OAV101 IT against a procedure that mimics drug administration without delivering active treatment. As the firm noted in a press release, the trial successfully met its primary endpoint by demonstrating a clinically meaningful increase from baseline in the Hammersmith Functional Motor Scale – Expanded (HFMSE) scores among participants treated with OAV101 IT compared to sham controls.
Key highlights from the STEER trial
The trial demonstrated statistically significant improvements in motor function in terms of HFMSE measures. This achievement in the primary endpoint is noteworthy given the trial’s focus on treatment-naïve patients aged 2 to <18 years with Type 2 SMA who could sit but had never walked independently.
In addition, the treatment led to an improvement in motor functions for some patients. As noted by Dr. Crystal Proud, Principal Investigator at Children’s Hospital of the King’s Daughters, this improvement could help patients maintain critical functions. “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,” said Proud in a press release.
The summary table below was found in a press release:
| Overalla Scemblix (n=201) vs. IS SoC TKIs (n=204) |
Imatinib stratumb Scemblix (n=101) vs. imatinib (n=102) |
2G TKI stratumc Scemblix (n=100) vs. 2G TKIs (n=102) |
||
| Key secondary endpoints | MMR rates at week 96 |
74.1% vs. 52% | 76.2% vs. 47.1% | |
| Secondary endpointsd | MMR rates at week 96 |
72% vs. 56.9% | ||
| MR4 at week 96 |
48.8% vs. 27.5% | 52.5% vs. 23.5% | 45% vs. 31.4% | |
| MR4.5 at week 96 |
30.9% vs. 17.7% | 35.6% vs. 11.8% | 26% vs. 23.5% |
a All patients receiving Scemblix (n=201) or investigator-selected SoC TKIs (n=204). Treatment difference after adjusting for pre-randomization selected TKI and EUTOS long-term survival (ELTS) risk groups at baseline.
b The 203 patients within the pre-randomization-selected imatinib stratum were randomized to receive either Scemblix (n=101) or imatinib (n=102). Treatment difference after adjusting for ELTS risk groups at baseline.
c The 202 patients within the pre-randomization selected 2G TKIs stratum were randomized to receive either Scemblix (n=100) or 2G TKIs (n=102: nilotinib, 48%; dasatinib, 41%; bosutinib, 11%).
d Secondary endpoints were not powered for statistical significance.
Background and context
SMA is a rare, genetic neuromuscular disease that leads to progressive muscle weakness and atrophy, often affecting swallowing, breathing, and basic movement. It stems from a mutation or deletion in the SMN1 gene and affects patients across a spectrum of severity. Historically, treatment has tended to focus on treating infants early to prevent irreversible motor neuron loss. Consequently, there has been a significant unmet need for older SMA patients.
Gene therapy with OAV101 IT delivers a functional copy of the SMN1 gene via an AAV9 vector directly into the central nervous system. This approach aims to restore SMN protein expression in older patients who may already have some degree of motor impairment or established disease progression.
Next steps for Novartis
Novartis plans to share the full STEER results with global regulatory authorities in 2025, including FDA. Novartis plans on sharing full data and additional analyses at a major medical conference next year.
If approved, OAV101 IT would be the first one-time, intrathecal gene therapy for older children and adolescents living with SMA.
More information on the Phase 3 NCT04971226 and Phase 2 NCT05384587 are available from clinicaltrials.gov.
Filed Under: Cell & gene therapy, Neurological Disease, Rare disease, Regulatory affairs
