One-Time Gene Replacement Therapy with Zolgensma Demonstrates Transformational Benefit For Spinal Muscular Atrophy Patients Interview with:

Sitra Tauscher-Wisniewski,

Dr. Tauscher-Wisniewski,

Sitra Tauscher-Wisniewski, MD
Vice President Clinical Development & Analytics
Novartis Gene Therapies What is the background for this study? Would you briefly describe the condition of Spinal muscular atrophy (SMA)?

Response: At the 2023 Muscular Dystrophy Association Conference, we presented new data from two of our  Long-Term Follow-Up (LTFU) studies, LT001 and LT002, which show the continued efficacy and durability of Zolgensma across a range of patient populations, with an overall benefit-risk profile that remains favorable. LT001 is a 15-year ongoing observational LTFU study following the Phase 1 START patients, who were the very first patients to receive our gene replacement therapy. LT-002 is a voluntary Phase 4 15-year ongoing follow-up safety and efficacy study of Zolgensma IV and investigational intrathecal (IT) OAV101 in patients previously treated in the Phase 3 IV studies (STR1VE-US, STR1VE-EU, STR1VE-AP, SPR1NT) and the Phase 1 IT study (STRONG).

Spinal muscular atrophy (SMA) is a rare, devastating genetic disease that leads to progressive muscle weakness, paralysis, and when left untreated in one of its most severe forms (SMA Type 1), permanent ventilation or death in 90% of cases by age 2. It is caused by a lack of a functional survival motor neuron 1 (SMN1) gene, and in the most severe forms results in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement. How does ZOLGENSMA differ from other treatments for SMA? Is it a one time or lifetime therapeutic treatment? Costs?

Response: Zolgensma is the only gene therapy for SMA and the only SMA treatment designed to directly address the genetic root cause of the disease by replacing the function of the missing or non-working SMN1 gene with a single, one-time dose. All other approved SMA therapies work on the backup gene, SMN2, and require repeated dosing over a patient’s lifetime.

Zolgensma is consistently priced based on the value it provides to patients, caregivers and health systems, as a one-time treatment with evidence of durability of efficacy now up to 7.5 years post dosing. In the U.S., Zolgensma is priced at around 50% less than multiple established benchmarks, including the 10-year cost of current standard in chronic SMA treatment. What are the main findings?

Response:  Latest data show that patients treated with Zolgensma survived, maintained, and in some cases gained, motor-milestones in the follow-up period, showing continued efficacy and durability across a range of patient populations. Notably, highlighting the remarkable durability of Zolgensma, data from LT-001, showed that up to 7.5 years post-dosing, children who were treated after presenting symptoms of SMA maintained all previously achieved milestones.

Interim results from the 15-year LT-002 study show 100% of children treated in the presymptomatic IV cohort either maintained the highest milestone achieved during the parent study (walking alone) or achieved the milestone by the data cut off. What should readers take away from your report?

Response: The LTFU data underscore the transformational and sustained benefit of Zolgensma as an essential one-time gene therapy for the treatment of SMA, providing further reassurance to patients, caregivers and the scientific community. Additionally, findings from the RESTORE registry continue to highlight the importance of early identification and intervention to optimize outcomes for all patients with SMA, with results showing that patients with four or more copies of the SMN2 gene treated with Zolgensma alone attained improvements in motor function and achieved new milestones. Adverse events experienced by these patients were also found to be consistent with previously reported safety findings. What recommendations do you have for future research as a results of this study?

Response: We are encouraged by this latest data and are continuing to evaluate gene therapy for SMA in different patient populations to bring the transformative impact of this treatment to more members of the SMA community. Is there anything else you would like to add? Any disclosures?

Response: Our priority remains focused on adding to the growing body of evidence for Zolgensma as a monotherapy that has demonstrated transformative efficacy, consistent safety and emerging long-term durability across a variety of patients with SMA. To date, more than 3,000 children with SMA have been treated with Zolgensma across clinical trials, managed access programs and in the commercial setting.


  1. Mendell J. et al. Long-Term Follow-Up of Onasemnogene Abeparvovec Gene Therapy in Symptomatic Patients with Spinal Muscular Atrophy Type 1. Abstract presented at the 2023 MDA Clinical & Scientific Conference. 19-22 March 2023.
  2. Connolly A. et al. Intravenous and Intrathecal Onasemnogene Abeparvovec Gene Therapy in Symptomatic and Presymptomatic Spinal Muscular Atrophy: Long-Term Follow-Up Study. Abstract presented at the 2023 MDA Clinical & Scientific Conference. 19-22 March 2023.
  3. Finkel R. et al. Outcomes in Patients with Spinal Muscular Atrophy and Four or More SMN2 Copies Treated with Onasemnogene Abeparvovec: Findings from RESTORE Registry. Abstract presented at the 2023 MDA Clinical & Scientific Conference. 19-22 March 2023. 

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Last Updated on March 29, 2023 by Marie Benz