Pharmaceutical giant Novartis has unveiled comprehensive clinical data supporting its application for a new spinal muscular atrophy (SMA) gene therapy, positioning the treatment as a potential successor to its existing therapy Zolgensma.
The experimental drug, OAV101, contains identical active ingredients to Zolgensma but is administered directly into the spine rather than intravenously. While Zolgensma’s use is currently restricted to patients under two years old, OAV101 aims to serve a broader patient population, particularly older children with moderate SMA who haven’t previously received targeted treatments.
Recent results from the pivotal STEER trial demonstrated significant improvements in motor function among patients receiving OAV101 compared to those given a placebo. Over a one-year period, treated patients showed a 2.39-point improvement on a standardized 66-point motor function scale, while the control group recorded only a 0.51-point increase. Though secondary endpoints consistently favored OAV101, they did not reach statistical significance.
Safety profiles between the treatment and control groups were comparable, with upper respiratory infections and fever emerging as the most frequent side effects. Serious adverse events included pneumonia and vomiting in the OAV101 group, while the control group experienced pneumonia and lower respiratory tract infections.
Liver safety, a crucial concern in gene therapy development, showed promising results. The study reported infrequent and mostly mild, temporary increases in transaminase levels, with no cases meeting Hy’s law criteria for severe liver damage risk – a particularly relevant finding given past fatal liver failure cases associated with Zolgensma.
Additional support for OAV101’s efficacy comes from the STRENGTH trial, which studied 27 patients who had previously discontinued other SMA treatments. Results indicated the therapy helped stabilize motor function, though all participants experienced at least one adverse event, with common cold, fever, and vomiting being most frequent.
Dr. Crystal Proud, a pediatric neurologist leading research at Children’s Hospital of the King’s Daughters in Virginia, emphasized that the combined results from both trials suggest OAV101 could represent a significant treatment advancement for SMA patients.
Novartis has maintained its commitment to OAV101 despite earlier development setbacks in 2019 and 2020. CEO Vas Narasimhan recently projected annual sales potential of $3 billion for the therapy, anticipating a launch trajectory similar to Zolgensma’s rapid initial adoption followed by steady-state sales.
The company’s Chief Medical Officer, Shreeram Aradhye, highlighted how the STEER results strengthen the case for OAV101 as a one-time treatment option that could benefit a wide range of SMA patients. Novartis plans to submit its approval application by the end of June.
The development represents a significant step forward in expanding treatment options for SMA patients, particularly those who fall outside current therapeutic parameters. If approved, OAV101 would offer a single-dose alternative for older children with moderate SMA, potentially filling an important gap in current treatment options.
Narasimhan expressed confidence in the therapy’s market potential, suggesting that the combination of one-time administration and demonstrated efficacy on standard measurement scales, coupled with a well-understood safety profile, would prove compelling to both physicians and patients.