Pharmaceutical giant Novartis has unveiled detailed clinical trial results supporting its bid to secure broad market approval for a new spinal muscular atrophy (SMA) gene therapy. The experimental treatment, OAV101, contains the same active component as the company’s existing therapy Zolgensma but is administered directly into the spine rather than intravenously.
The latest data comes from the STEER study, which evaluated OAV101 in children over two years old with moderate SMA who had not previously received targeted treatments like Zolgensma, Spinraza, or Evrysdi. The trial demonstrated that patients receiving OAV101 achieved a 2.39-point improvement on a motor function scale, significantly outperforming the 0.51-point gain observed in the control group.
Secondary endpoints consistently favored OAV101, though these did not reach statistical significance. Safety profiles were comparable between treatment and control groups, with upper respiratory infections and fever emerging as the most common side effects. Serious adverse events included pneumonia and vomiting in the OAV101 group, while the control group experienced pneumonia and lower respiratory tract infections.
Notably, the study showed infrequent and generally mild, temporary increases in liver enzymes, with no cases meeting “Hy’s law” criteria for severe liver damage risk. This finding is particularly relevant given previous concerns about liver complications in gene therapies using adeno-associated viruses as delivery vehicles, including two fatal cases of acute liver failure in Zolgensma patients.
Additional support for OAV101’s potential comes from the STRENGTH trial, an open-label study involving 27 participants who had previously discontinued Spinraza or Evrysdi treatment. 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 at Children’s Hospital of the King’s Daughters in Virginia and principal investigator, suggested the combined STRENGTH and STEER results point to OAV101 as a potentially significant treatment option for SMA patients.
Novartis has maintained its commitment to developing OAV101 despite earlier 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 uptake followed by steady-state sales.
The company plans to submit its approval application by the end of June, positioning OAV101 as a one-time treatment option for a broader SMA patient population than currently served by Zolgensma, which is limited to patients under two years of age. Novartis’s chief medical officer, Shreeram Aradhye, emphasized that the STEER results strengthen the company’s confidence in OAV101’s potential to significantly impact SMA treatment through a single dose delivering continuous benefit.
This development represents a significant step in Novartis’s strategy to expand its presence in the SMA treatment landscape, potentially offering a new therapeutic option for patients who currently have limited treatment choices. The company’s approach focuses on highlighting the therapy’s one-time administration and established efficacy measures to appeal to both healthcare providers and patients.