RARE Daily

Novartis Reports Long-Term Efficacy of Zolgensma

March 22, 2023

Rare Daily Staff

Novartis presented new data from two-long terms studies of Zolgensma, its one-time gene therapy for the treatment of neuromuscular disease spinal muscular atrophy, that showed continued efficacy and durability of Zolgensma across a range of patient populations for up to 7.5 years and a favorable benefit-risk profile.

The data were among a Zolgensma data set presented during the 2023 Muscular Dystrophy Association Clinical and Scientific Conference.

Spinal muscular atrophy (SMA) is a rare, genetic disease and a leading genetic cause of infant death. It is caused by the lack of a functional SMN1 gene. The most severe forms of SMA results in the rapid and irreversible loss of motor neurons, affecting muscle functions including breathing, swallowing and basic movement. Severity varies across a spectrum of types corresponding to the number of copies of the back-up SMN2 gene. The majority of patients with two copies of SMN2 develop Type 1, the most common form accounting for 60 percent of cases. Type 1 is severe and, if left untreated, leads to death or the need for permanent ventilation by the age of two in more than 90 percent of cases. Most patients with three copies of SMN2 develop Type 2, accounting for 30 percent of cases. If left untreated, patients with Type 2 are unable to walk and will require a wheelchair, and more than 30 percent will die by age 25.

Zolgensma is the only approved gene therapy for the treatment of 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 to halt disease progression through sustained SMN protein expression with a single, one-time IV infusion. Zolgensma is now approved in more than 47 countries and more than 3,000 patients have been treated with Zolgensma globally. 

The Zolgensma data from LT-001, an ongoing 15-year long-term follow up study of patients who completed the phase 1 START study, showed children who were treated after presenting symptoms of SMA maintained all previously achieved motor milestones. During the time of LT-001, three additional patients also achieved the key milestone of standing with assistance.

“These children now have an improved quality of life, vastly different from what would have been expected for them if they had not received treatment. I am excited to see the new possibilities that open up to the children, their families and others who may now be able to receive this treatment,” said Jerry Mendell of Nationwide Children’s Hospital.

Interim results from the 15-year LT-002 study, which includes both pre-symptomatic and symptomatic patient populations, as well as intravenous (IV) and intrathecal (IT) administration methods were also presented, with all patients maintaining motor milestones achieved during their respective parent studies in the follow-up period.

Results from the IV cohort, which included 63 patients, demonstrated how a single administration of Zolgensma provided consistent, substantial and durable efficacy over time. Notably, in the pre-symptomatic IV cohort, all children either maintained the highest milestone achieved during the parent study (walking alone) or achieved the milestone by the data-cut off. In total, six patients treated prior to SMA symptom onset and 16 treated after SMA symptom onset achieved new motor milestones in the follow-up period.

All 18 children in LT-002 who were treated with one-time investigational OAV101 IT, were alive, free from permanent ventilation and continued to show incremental gains in motor function as of the May 2022 data cut-off. Five of 16 patients who had a milestone assessment achieved new milestones during the long-term follow-up period, such as crawling, walking or standing with assistance.

The majority of patients in LT-002 (70.4 percent) never received add-on therapy (76.2 percent of the IV cohort, 50 percent of the investigational OAV101 IT cohort). Among patients in the intravenous cohort, 24 of 25 patients treated before symptom onset achieved the motor milestone of walking alone prior to or without add-on therapy, and 30 of 32 patients treated after SMA symptom onset achieved the milestone of sitting without support prior to or without add-on therapy.

“Data from the LT-001 and LT-002 studies showed that, regardless of the patient’s symptomatic status at the time of treatment, Zolgensma IV is an effective and durable treatment option,” said Sitra Tauscher-Wisniewski, vice president of clinical development and analytics for Novartis Gene Therapies. “As the number of patients treated with gene therapy around the world continues to grow, our goal is that more patients, and even new SMA patient populations, will be able to experience the transformative impact of this treatment.”

Photo: Sitra Tauscher-Wisniewski, vice president of clinical development and analytics for Novartis Gene Therapies

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