OAV101 in SMA patients demonstrates improved motor function, disease progression
Results were from the phase 3 STEER study among a broad population of patients with SMA aged 2 to under 18 years.
OAV101 in SMA patients demonstrates improved motor function, disease progressionLatest revision | Image Credit: © Dzmitry - © Dzmitry - stock.adobe.com.
On March 19, 2025, Novartis announced positive phase 3 data for investigational onasemnogene abeparvovec (OAV101 IT), which led to improvements of motor function among a broad population of patients aged 2 to younger than 18 years with spinal muscular atrophy (SMA).1
According to a press release, OAV101 IT treatment led to a statistically significant 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE)—a SMA-specific assessment of motor ability and disease progression—in the phase 3 STEER study (NCT05089656).2 The nearly 2.4-point improvement was compared to 0.51 points in a sham control arm (P = 0.0074).1
Additionally, OAV101 IT in patients who discontinued treatment with nusinersen or risdiplam demonstrated stabilization of motor function over 52 weeks of follow-up, according to the phase 3b STRENGTH study (NCT05386680),3 stated Novartis.1
"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, MD, in a statement.
Proud is a pediatric 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," added Proud.
Trial data
STEER study
According to Novartis, the investigational gene therapy is designed to address the genetic root cause of disease by replacing the nonworking SMN1 gene with a single dose.
The STEER study evaluated efficacy and safety in treatment naïve patients with SMA Type 2, in patients aged 2 to less than 18 years. Patients were able to sit, but had never walked independently. The sham control was designed to mimic the administration of an investigational drug, without delivering any active treatment.
There were 126 patients in the trial, of which 75 received OAV101 IT and 51 the sham procedure. At dosing, the mean age was 5.89 (2.1–16.6) years in the treatment group and 5.87 (2.4–14.2) years in the sham arm.
Overall, the trial met the primary endpoint of change from baseline to 52 weeks in HFMSE score, and "all secondary endpoints consistently favor OAV101 IT, despite not achieving statistical significance due to the pre-planned multiple testing procedure," stated Novartis.
Overall incidence of adverse events, serious adverse events, and adverse events of special interest were similar between both groups.
The most common adverse events in both groups in the study were upper respiratory tract infection and pyrexia. Pneumonia and vomiting were the most common serious adverse event in the treatment group, with pneumonia and lower respiratory tract infection the most common in the sham group.
"Instances of transaminase increases were infrequent; most were low-grade and transient. There were no cases of Hy’s law," stated Novartis.
STRENGTH study
In this open-label study, safety, tolerability, and efficacy of OAV101 IT was assessed in the same age group of patients who discontinued treatment with nusinersen or risdiplam. In the study, 27 patients were enrolled with a mean (range) age of 7.4 years (2.4-17.7). Mean duration of prior risdiplam and nusinersen treatment were 2.98 and 4.32 years, respectively.
Safety profile for OAV101 IT was consistent with the STEER study, the motor endpoint of efficacy, HFMSE, demonstrated stabilization for the overall study population over 52 weeks, and the increase from baseline to 52 weeks in HFMSE least squares (LS) total score was 1.05, according to results shared by Novartis.
"The data presented today from our OAV101 IT program reinforce 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,” said Shreeram Aradhye, MD, president, Development and chief medical officer, Novartis. “Together with patients, caregivers and healthcare professionals, we are committed to continuing to advance our mission to lead innovation in SMA treatment and broaden therapy options with our gene replacement therapies.”
References:
1. New Novartis Phase III data demonstrate meaningful efficacy and safety results of intrathecal onasemnogene abeparvovec in broad patient population with SMA. Novartis. Press release. March 19, 2025. Accessed March 19, 2025. https://www.novartis.com/news/media-releases/new-novartis-phase-iii-data-demonstrate-meaningful-efficacy-and-safety-results-intrathecal-onasemnogene-abeparvovec-broad-patient-population-sma
2. The STEER research study. Novartis. Accessed March 19, 2025. https://www.novartis.com/clinicaltrials/NCT05089656
3. Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam (STRENGTH). ClinicalTrials.gov. Updated January 10, 2025. Accessed March 19, 2025. https://clinicaltrials.gov/study/NCT05386680
