AveXis, a gene therapy company of Novartis, has recently released the latest data from the Phase I / II STRONG study of one-time gene therapy Zolgensma (onasemnogene abeparvovec, AVXS-101) for intrathecal administration of type 2 spinal muscular atrophy (SMA).
The results showed that pediatric patients with type 2 SMA (2 years ≤ age <5 years) treated with a single dose of intrathecal Zolgensma at dose B (1.2 x 10 to the 14th power vg) reached the primary efficacy endpoint: Hammersmith Functional Exercise Extension The scale (HFMSE) score increased significantly from the baseline level by an average of 6.0 points, twice the threshold of clinical significance determined in the previous SMA study, reflecting the improvement of 3-6 skills. In addition, during the study period, almost all patients (92%) at any follow-up after baseline examination, HFMSE achieved a clinically significant increase of ≥3 points, showing sustained remission and significant compared with natural history control Difference (p <0.0001).
The increase observed in the HFMSE score reflects the preservation of motor neurons associated with the key muscle groups affected in type 2 SMA, allowing motor development such as rolling and torso control during sitting and sitting from lying to sitting Transition. Contrary to these findings, according to natural history, patients with untreated type 2 SMA usually have a steady decline in motor function, and more than 30% of patients die before the age of 25. In terms of safety, the adverse events observed in the STRONG study were consistent with the Zolgensma IV (intravenous infusion) project. There were no reports of deaths and no new safety signals were found.
These data were announced at a virtual clinical trial meeting hosted by the Muscular Dystrophy Association (MDA) recently. The meeting was originally planned to be held after the MDA annual meeting in 2020, but was cancelled due to the impact of the new coronavirus pneumonia (COVID-19).
Dave Lennon, president of AveXis, said: "Almost all patients evaluated on the gold standard Hammersmith scale have obtained clinically meaningful therapeutic responses. Through continuous and stable SMN protein expression, they consistently show improved motor function. In 2- Among patients with type 2 SMA between the ages of 5 and 5 years old, the data from the STRONG study showed that Zolgensma has the best characteristics of its kind, and the patient's motor function is significantly improved after a single intrathecal administration. We look forward to sharing these data with regulatory agencies To further discuss the registration of intrathecal Zolgensma. "
Olga Santiago, chief medical officer of AveXis, said: "Due to the continuous evolution of treatment options, older type 2 SMA patients now hope to achieve meaningful improvements in motor function, enable them to carry out important activities, and make them more independent Road. Considering these powerful treatment responses, data from the STRONG study suggest that intrathecal injection of Zolgensma may become a new one-time treatment option for patients and their clinicians. "
Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disease. Due to the lack of a 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 number one killer of genetic diseases among infants and young children under 2 years of age. SMA type 1 is the most common type, accounting for about 60% of all cases. Without treatment, more than 90% of patients will die at the age of 2 or require permanent ventilation.
Zolgensma was approved by the US FDA in May 2019 and became the world's first gene therapy for SMA. The drug is suitable for: SMA patients under 2 years of age.
Zolgensma is a one-time gene therapy that aims to solve the genetic root of SMA disease by replacing the function of the missing or non-functional SMN1 gene. After a single intravenous infusion (IV) administration, Zolgensma introduces a functional copy of the SMN gene into the patient's cells and continuously expresses the SMN protein to stop the disease process, thereby improving the patient's quality of life in the long term.
Clinical studies have shown that in patients with symptomatic and pre-symptomatic SMA, Zolgensma single infusion therapy shows significant clinically significant therapeutic benefits, including prolonging event-free survival and achieving motor milestones not seen in the natural history of the disease.