Novartis’ OAV101 IT Improves or Stabilizes Motor Function in Patients With Spinal Muscular Atrophy
OAV101 IT is a version of Zolgensma that is delivered directly to the spine.
Novartis’ OAV101 IT, an investigational intrathecally-delivered version of the marketed gene therapy onasemnogene abeparvovec (Zolgensma), has demonstrated the ability to improve patient scores on the Hammersmith Functional Motor Scale Expanded (HFMSE).1 The data, which come from the phase 3 STEER clinical trial (NCT05089656), were presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas.
The STEER study includes treatment-naive children aged 2 to less than 18 years who could sit but had not ever walked independently, and evaluated OAV101 IT against a placebo procedure. It was found that patients who received the gene therapy (n = 75) achieved a 2.39-point improvement on the HFMSE, whereas those who received the placebo (n = 51) showed only a 0.51 point improvement on the HFMSE (P=0.0074); as such, STEER met its primary end point. Novartis pointed out that results for the secondary end points did not reach statistical significance because of the preplanned multiple testing procedure, but that these findings “consistently favor” OAV101 IT. Patients in the treatment group were aged 2.1 to 16.6 years (mean, 5.89) and patients in the placebo group were aged 2.4 to 14.2 years (mean, 5.87)
With regard to safety, adverse events (AEs), serious AEs (SAEs), and AEs of special interest were reported to have a similar incidence between the treatment group and the placebo group. Upper respiratory tract infection and pyrexia constituted the most common AEs in both groups. Pneumonia and vomiting constituted the most common SAEs in patients who received the gene therapy, whereas pneumonia and lower respiratory tract infection constituted the most common SAEs in patients who received the placebo. Novartis stated that increased transaminase cases did not occur frequently, and those cases that did occur were for the most part transient and low grade. Hy’s law cases did not occur in any patients.
In addition to the STEER data, Novartis also presented data from the phase 3b STRENGTH clinical trial (NCT05386680) evaluating OAV101 IT. STRENGTH treated children aged 2 to less than 18 years who had ceased receiving standard of care treatment in the form of nusinersen (Spinraza) or risdiplam. The trial included 27 patients aged 2.4 to 17.7 years of age (mean, 7.4).The patients who had previously been treated with risdiplam had been on that treatment for a mean of 2.98 years and the patients who had previously been treated with nusinersen had been on that treatment for a mean of 4.32 years. At 52 weeks of follow-up, patients showed a 1.05 increase in HFMSE least squares (LS) total score from baseline. Novartis stated that the overall population in the trial showed stabilization of HFMSE over 52 weeks.
With regard to safety it was noted that 48.1% of patients (n=13) had AEs deemed related to the treatment, but that no AEs in the study were fatal or led to discontinuation of participation. Common cold, pyrexia and vomiting constituted the most common AEs. All patients in STRENGTH had at least 1 AE.
“In the STEER study evaluating treatment-naïve patients, OAV101 IT demonstrated a statistically significant improvement in motor function across a broad SMA population,” principal investigator Crystal Proud, MD, a pediatric neurologist at Children's Hospital of the King's Daughters, said in a statement.1 “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.”
OAV101 IT is differentiated from the FDA-approved version of Zolgensma, which is delivered systemically, in that it is delivered directly to the spine. Both versions utilize an adeno-associated virus 9 vector.
“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,” Shreeram Aradhye, MD, the president of development and chief medical officer at Novartis, added to the statement.1 “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.”
Earlier this year, CGTLive® spoke to Barry J Byrne, MD, PhD, the chief medical advisor of MDA and a physician-scientist at the University of Florida, about what to look forward to at the then-upcoming 2025 MDA Clinical & Scientific Conference. Byrne mentioned SMA and Zolgensma during the interview.
“Really, this is the era of therapies for neuromuscular diseases,” Byrne told CGTLive. “In the past year, we saw an additional few strategies that are transformative in the care of boys with Duchenne muscular dystrophy and we have continued to make advances in SMA care following on the enormous success of the release of Zolgensma in 2019. There are now more than 3,000 patients who've received that gene therapy product, and we'll see more new ideas about gene therapy strategies for both central nervous system disorders, as well as muscle disorders that affect this population.”
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