Zolgensma Continues to Show Therapeutic Benefit in SMA Type 1


Nearly two-thirds of patients achieved developmental motor milestones not observed in the natural history of SMA Type 1 at a mean duration of follow-up of 10.6 months.

Eugenio Mercuri, MD, PhD

Newly released interim data from the phase 3 STR1VE-EU clinical trial of onasemnogene abeparvovec (Zolgensma; Novartis) demonstrated the treatment’s significant therapeutic benefit in patients with spinal muscular atrophy (SMA) Type 1.1

Patients within the study experienced event-free survival, rapid and sustained improvement in motor function, and motor milestone achievements. Evidence of these achievements was also found in patients with more aggressive disease at baseline compared to those in previous trials. The interim data was accurate as of December 31, 2019, and was presented recently as part of the World Muscle Society (WMS) 2020 Virtual Congress.

Achievement of milestones not previously observed in the natural history of SMA Type 1 was observed in 21 (65.6%) patients within the study. Among them, 6 (18.8%) achieved the primary end point by sitting independently for ≥10 seconds.

“We are seeing further evidence of the potential of Zolgensma to effectively halt motor neuron loss following a one-time, intravenous infusion. In STR1VE-EU, patients achieved rapid improvements in motor function following treatment with Zolgensma, and most have already achieved motor milestones not observed in the natural history of SMA Type 1,” Eugenio Mercuri, MD, PhD, professor of pediatric neurology, Catholic University, Rome, said in a statement.

The additional milestone of gaining head control was achieved by 20 (66.7%) patients. As well, 8 (25%) patients were able to roll back to sides and 1 patient was able to stand with assistance, crawl and walk with assistance.

READ MORE: Vamorolone Improves Motor Function in Patients With DMD

At last visit before the data cutoff, 31 of 32 (97%) patients in the intent-to-treat (ITT) population survived event-free, including 30 (93.8%) who could have reached 10.5 months of age and 18 (56.3%) who could have reached 13.6 months of age. For context, the patients in STR1VE-EU were between 6.9 and 18.6 months of age, and mean duration in the study was 10.6 months (range 1.8–15.4).

Events were defined as the need for tracheostomy or the requirement of ≥16 hours of respiratory assistance per day through non-invasive ventilatory support for ≥14 consecutive days in the absence of an acute reversible illness, excluding peri-operative ventilation. Novartis noted that untreated natural history indicates that only 50% and 25% of babies with SMA Type 1 will survive event-free by the time they reach 10.5 months of age and 13.6 months of age, respectively.

Investigators also documented that 31 of the 33 (93.9%) of patients were able to swallow thin liquids and 10 (30.3%) patients required feeding support at baseline. Additionally, 9 of 30 (27.3%) patients required ventilatory support at baseline.

Investigators noted that STR1VE-EU is distinct in its inclusion and exclusion criteria and baseline clinical characteristics compared with START or STR1VE-US. This was explained by a portion of patients who had a more severe disease phenotype at baseline, including lower CHOP-INTEND scores and the need for nutritional and ventilatory support. The mean Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score increase was 5.9 points from baseline (n = 31) which was observed as early as 1-month post-dosing. Scores continued to grow to 10.1 points at 3 months (n = 29) post-dosing, and 13.3 points at 6 months (n = 27) post-dosing.

In total, 21 (65.6%) patients in the study achieved and maintained a CHOP-INTEND score of ≥40 points and 12 children (37.5%) were able to achieve a score of ≥50. Novartis noted that according to natural history, untreated patients almost never achieve a CHOP-INTEND score of ≥40.

One patient had to discontinue the study due to a serious event of hypoxic-ischemic brain damage and respiratory distress that resulted in death but was found to be unrelated to treatment with Zolgensma. Adverse events (AEs) were found in 32 of 33 patients, including 6 patients who experienced serious AEs related to Zolgensma treatment.

“These strong interim results from the STR1VE-EU clinical trial continue to demonstrate consistent and significant therapeutic benefit in patients with SMA Type 1, the most common form of the disease, adding to the robust body of clinical evidence for Zolgensma,” Shephard Mpofu, MD, SVP, chief medical officer, Novartis, said in a statement. “With more than 600 patients now treated, including some more than five years post-treatment and more than five years old, these data further reinforce the transformative benefit a one-time dose of Zolgensma has on SMA patients.

The FDA approved Zolgensma for the treatment of SMA in pediatric patients <2 years of age with mutations in the SMN1 gene. It became the first and only gene therapy FDA-approved for SMA, including patients who are presymptomatic. The basis of the approval was from the ongoing phase 3 STR1VE trial as well as the phase 1 START trial, which included patients with SMA Type 1 who showed symptoms at <6 months2

1. Zolgensma data including patients with more severe SMA at baseline further demonstrate therapeutic benefit, including prolonged event-free survival, increased motor function and milestone achievement. News release. Basel, Switzerland: Novartis. October 1, 2020. Accessed October 7, 2020. https://www.globenewswire.com/news-release/2020/10/01/2101849/0/en/Zolgensma-data-including-patients-with-more-severe-SMA-at-baseline-further-demonstrate-therapeutic-benefit-including-prolonged-event-free-survival-increased-motor-function-and-mile.html
2. AveXis receives FDA approval for Zolgensma®, the first and only gene therapy for pediatric patients with spinal muscular atrophy (SMA) [news release]. Basel, Switzerland: Novartis. May 24, 2019. Accessed October 7, 2020.
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