Novartis’ Zolgensma Shows Robust Efficacy in Type 2 SMA Patients via Intrathecal Administration in Phase I/II STRONG Study
Mar 25, 2020 20:30
CST Updated
20:30
Novartis
Drug Development and Manufacturing
March 25, 2020/BioValleyBIOON/--Novartis(under Novartis)Gene TherapyAveXis recently announced updated data from the Phase I/II STRONG study evaluating intrathecal administration of the one-time gene therapy Zolgensma (onasemnogene abeparvovec, AVXS-101) in patients with Type 2 spinal muscular atrophy (SMA).
The results demonstrated that pediatric patients with Type 2 SMA (aged ≥2 to <5 years) treated with a single intrathecal injection of Zolgensma at Dose B (1.2 x 10^14 vg) achieved the primary efficacy endpoint: the Hammersmith Functional Motor Scale Expanded (HFMSE) score increased by a mean of 6.0 points from baseline, which is twice the threshold for clinical significance established in previous SMA studies, reflecting an improvement in 3–6 motor skills. Furthermore, during the study period, nearly all patients (92%) achieved a clinically meaningful increase of ≥3 points in HFMSE scores at any follow-up assessment after baseline, demonstrating sustained benefit and a significant difference compared to the natural history control group (p<0.0001).
The observed increase in HFMSE scores reflects the preservation of motor neurons associated with key muscle groups affected in type 2 SMA, enabling motor development such as trunk control during rolling and sitting, as well as the transition from supine to sitting positions. In contrast to these findings, untreated patients with type 2 SMA typically experience a steady decline in motor function consistent with the natural history of the disease, with more than 30% of patients dying before the age of 25. Regarding safety, the adverse events observed in the STRONG study were consistent with those reported in the Zolgensma IV (intravenous infusion) program; no deaths were reported, and no new safety signals were identified.
These data were recently presented at a virtual event hosted by the Muscular Dystrophy Association (MDA)Clinical TrialMeetingpublished above. The meeting was originally scheduled to be held after the 2020 MDA Annual Conference, but it was canceled due to the impact of the novel coronavirus disease (COVID-19).
Dave Lennon, President of AveXis, stated, “Nearly all patients assessed using the gold-standard Hammersmith Scale demonstrated clinically meaningful treatment responses, with consistent improvements in motor function achieved through sustained and stable SMN protein expression. In patients with Type 2 SMA aged 2 to 5 years, data from the STRONG study showed that Zolgensma has a best-in-class profile, with significant improvement in motor function following a single one-time intrathecal administration. We look forward to sharing these data with regulatory authorities to further discuss the registration of intrathecal Zolgensma.”
Olga Santiago, Chief Medical Officer of AveXis, stated, “As treatment paradigms continue to evolve, older patients with Type 2 spinal muscular atrophy (SMA) now hope to achieve meaningful improvements in motor function, enabling them to perform essential activities and embark on a path toward greater independence. In light of these robust treatment responses, data from the STRONG study suggest that intrathecal administration of Zolgensma may represent a new one-time treatment option for patients and their clinicians.”
Spinal Muscular Atrophy (SMA) is a rare hereditary neuromuscular disease. Due to the lack of functional SMN1 gene, SMA leads to rapid and irreversible loss of motor neurons, affecting muscle function, including breathing, swallowing, and basic movement. SMA is the leading cause in infants under 2 years of age.HereditySMA is a fatal disease, with Type 1 SMA being the most common type, accounting for approximately 60% of all cases. Without treatment, more than 90% of patients will die or require permanent ventilation by the age of 2.
Zolgensma was approved in the United States in May 2019FDAApproved for market launch, it became the world’s first gene therapy for treating SMA. This drug is indicated for: SMA patients under 2 years of age.
Zolgensma is a one-time gene therapy designed to address the genetic root of spinal muscular atrophy (SMA) by replacing the function of the missing or nonfunctional SMN1 gene. Following a single intravenous (IV) infusion, Zolgensma delivers a functional copy of the SMN gene into the patient’s cells, enabling sustained expression of the SMN protein to halt disease progression and thereby improve patients’ quality of life over the long term.
Clinical studies have demonstrated that a single infusion of Zolgensma provides clinically significant therapeutic benefits in both symptomatic and pre-symptomatic patients with spinal muscular atrophy (SMA), including prolonged event-free survival and the achievement of motor milestones not observed in the natural history of the disease. (Bioon.com)