FDA approves Itvisma for patients 2 years and older with SMA, making it the first FDA-approved gene replacement therapy for this population.
The US Food and Drug Administration (FDA) approved Itvisma (onasemnogene abeparvovec-brve; Novartis) for children aged 2 years and older, adolescents, and adults with spinal muscular atrophy (SMA) who have a confirmed mutation in SMN1. According to Novartis, Itvisma is the first gene replacement therapy approved for this patient population. The product is administered as a 1-time fixed intrathecal dose that does not require adjustment by age or body weight.1
The therapy is designed to provide a functional copy of SMN1 to support sustained SMN protein expression. Novartis reports that treatment “can improve motor function, offering the potential to reduce the need for chronically administered treatment associated with other available therapies for this population.”
John W. Day, MD, PhD, professor of Neurology and Pediatrics at Stanford University, said, “The FDA’s approval of intrathecal onasemnogene abeparvovec is a game-changing advance, expanding the use of transformational gene replacement therapy for SMA across age groups.”1
The FDA approval was based primarily on results from the registrational Phase III STEER trial. In this study, Itvisma produced statistically significant improvements in motor function and stabilization of abilities not typically seen in the natural history of SMA. Effects were sustained over 52 weeks, and the therapy’s safety profile was consistent across trials. The most common adverse events were upper respiratory tract infection and pyrexia.
Crystal Proud, MD, a pediatric neurologist and principal investigator, noted that in STEER, “OAV101 IT demonstrated a statistically significant improvement in motor function across a broad SMA population.”2
The open-label Phase IIIb STRENGTH study evaluated patients who had discontinued nusinersen or risdiplam. The study demonstrated stabilization of motor function over 52 weeks, with the most common adverse events being common cold, pyrexia, and vomiting. No treatment-related deaths or discontinuations occurred.
Stakeholders emphasized the potential practical impact of a single-dose gene replacement therapy. Kenneth Hobby, president of Cure SMA, stated, “This new route of administration for a single dose of gene replacement therapy can mean so much more than what is measured by numbers on a functional motor scale – it could mean greater independence and freedom in activities of daily life.”
He added that the approval “represents real progress in expanding access for many older patients and addressing the unmet needs that remain in our community.”
SMA is caused by a missing or mutated SMN1 gene. Loss of SMN protein leads to degeneration of motor neurons and progressive muscle weakness. Approximately 9,000 individuals in the United States live with SMA, and unmet needs remain for older children, teens, and adults. Novartis indicated that providing a functional SMN1 gene through a single intrathecal dose may address some of these gaps.
Victor Bultó, president, Novartis US, said, “After redefining SMA care with the first gene replacement therapy for this challenging disease, we can now help address unmet needs across an even broader SMA population with the approval of Itvisma.”
According to Novartis, Itvisma will be available beginning in December. A support program is available to assist eligible patients with treatment initiation, coverage understanding, and potential financial assistance.
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