Shephard Mpofu, MD, the senior vice president and chief medical officer at Novartis Gene Therapies, offered his perspective on the latest phase 3 data of onasemnogene abeparvovec (Zolgensma) in SMA treatment.
In March 2022, new data from the phase 3 SPR1NT trial (NCT03505099) of onasemnogene abeparvovec (Zolgensma; Novartis Gene Therapies) showed promising results for the treatment among patients with spinal muscular atrophy (SMA) who were presymptomatic and had 3 copies of the SMN2 gene. Overall, the gene therapy was well-tolerated as well as efficacious.
The results of the multicenter, open-label study were presented at the 2022 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, March 13-16, in Nashville, Tennessee.1,2 All told, the dataset included 15 patients, showing that the primary and secondary end points were met with statistical significance compared with the cohort from the Pediatric Neuromuscular Clinical Research (PNCR) natural history data set (P <.001).
At the time of reporting, 100% of patients were alive, and none needed ventilatory or feeding tube support at any time during the study. Additionally, 100% of the cohort achieved the ability to stand alone—of which 93% (n = 14) did so within the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) developmental window. There were 14 patients who walked alone, 11 within the WHO-MGRS developmental window. All told, 100% of patients reported an adverse event (AE), and 53% (n = 8) had at least 1 treatment-related AE. A total of 3 patients reported serious AEs, though no serious AEs were considered treatment-related by the investigators.
To gain more context about these data and their significance for the clinical community, NeurologyLive® inquired with Shephard Mpofu, MD, senior vice president and chief medical officer, Novartis Gene Therapies. He offered his perspective on the data in detail.
Shephard Mpofu, MD: The completed Phase 3 SPR1NT data presented at MDA show that children with three copies of the SMN2 back-up gene treated presymptomatically achieved age-appropriate milestones, including standing and walking. This is a stark contrast with the natural progression of SMA. Without treatment, most children with three copies of the SMN2 back-up gene develop SMA Type 2, characterized by the inability to walk independently. Results from SPR1NT reinforce that early treatment is critical regardless of medication and further demonstrates the outstanding impact Zolgensma can have on children with SMA.
We are excited that the results from the SPR1NT trial once again confirm the transformative impact of Zolgensma for children with SMA, and now in patients who were treated presymptomatically.
Fourteen of 15 children (or 93%) went on to walk independently, most (11 of 15, or 73%) within the World Health Organization window of normal development. All 15 children met the primary end point of standing alone 3 or more seconds, including 14 of 15 (or 93%) within the WHO window of normal development. All children were free of feeding tube support and ventilatory support of any kind during the study, and no serious, treatment-related adverse events were reported
These results are in sharp contrast to the natural history of the disease—and they again reinforce the value of early diagnosis and treatment of SMA.
Zolgensma has demonstrated consistent, transformative, and clinically meaningful therapeutic benefit in presymptomatic and symptomatic SMA, including prolonged event-free survival and achievement of motor milestones unseen in natural history of the disease.
The data presented at MDA continue to reinforce the benefit of Zolgensma in the real-world setting, including in patients outside of our current clinical trial experience.
We believe that all patients diagnosed with SMA should be able to benefit from the transformative impact of gene therapy, and we continue to study its effect in patient groups where unmet needs remain. The data presented at MDA continue to reinforce the benefit of Zolgensma in the real-world setting, including in patients outside of our current clinical trial experience.
In addition to the SPR1NT data, Novartis also presented a descriptive post hoc analyses of START, STR1VE-EU and STR1VE-US that indicated children with SMA Type 1 achieved or maintained important measures of bulbar function following treatment with Zolgensma, including ability to speak; swallow and meet nutritional needs; and maintain airway protection. Bulbar motor neurons control muscles required for functions like swallowing, speaking, and chewing, and impairment from SMA can lead to choking, malnutrition, infection and death.
In April 2021, we announced plans to initiate SMART, a phase 3b clinical study to evaluate the safety and efficacy of Zolgensma in young children with SMA weighing 8.5 kg or more and 21 kg or less. Additionally, in August 2021, we announced plans to initiate STEER, a global pivotal phase 3 registration-enabling study to evaluate the clinical efficacy, safety, and tolerability of OAV101 intrathecal in treatment-naïve patients who are between 2 and 18 years of age, able to sit, but have never walked.
Transcript edited for clarity. For more coverage of MDA 2022, click here.