**Novartis has announced positive results from a late-stage programme of its experimental gene replacement therapy in patients with the rare neuromuscular disease spinal muscular atrophy (SMA).**
The phase 3 STEER study has been evaluating intrathecal onasemnogene abeparvovec (OAV101 IT) in treatment-naïve patients aged two to less than 18 years with SMA type 2 who were able to sit but had never walked independently.
The trial met its primary endpoint, with OAV101 IT demonstrating a statistically significant 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded, used to assess motor ability and disease progression, compared to a 0.51-point improvement in patients receiving a sham procedure.
Novartis also shared results from the open-label phase 3b STRENGTH study of OAV101 IT in SMA patients aged two to less than 18 years who had discontinued treatment with nusinersen or risdiplam, which showed stabilisation of motor function over 52 weeks of follow-up.
Safety findings were consistent in both treatment-naïve and treatment-experienced patients, Novartis said, adding that it is planning to file regulatory applications for OAV101 IT in the first half of this year.
Shreeram Aradhye, president, development and chief medical officer, Novartis, said: “The data presented… from our OAV101 IT programme reinforces our belief in this therapy, which has the potential to have a meaningful impact on a broad range of people with SMA through its continuous benefit via a one-time dose.”
SMA occurs in an estimated one in 10,000 infants globally and is caused by a lack of a functional SMN1 gene. This results in the irreversible loss of motor neurons, affecting muscle functions such as breathing, swallowing and basic movement.
OAV101 IT, administered as a one-time injection into the spine, is designed to directly address the genetic root cause of the disease by replacing the nonworking SMN1 gene.
“In the STEER study evaluating treatment-naïve patients, OAV101 IT demonstrated a statistically significant improvement in motor function across a broad SMA population,” said Crystal Proud, paediatric neurologist and a principal investigator at Children’s Hospital of the King’s Daughters.
“These results – paired with those in the STRENGTH study – support the potential for OAV101 IT to be a meaningful treatment option for people living with SMA with a goal of maintaining or improving motor function through a one-time therapy,” Proud added.