Itvisma approval ushers in era of therapeutic choice for SMA patients
Last month’s approval of Novartis‘ one-time gene therapy Itvisma (onasemnogene abeparvovec-brve) for people with spinal muscular atrophy (SMA) ages 2 and older is a milestone that “ushers in a new era of informed therapeutic choice,” according to Angela Lek, PhD, chief research officer at the Muscular Dystrophy Association (MDA).
“This approval is a reminder of what’s possible when we work together — and a motivator to keep pushing for safer, more effective, and more accessible treatments for every family,” Lek said in a written interview with SMA News Today.
Itvisma’s approval ‘a scientific milestone and a community milestone’
SMA is a genetic disease characterized by the degeneration and death of motor neurons, the nerve cells responsible for controlling movement. It is chiefly caused by mutations in the SMN1 gene. Gene therapy for SMA aims to deliver a healthy copy of the SMN1 gene to motor neurons, thus addressing the underlying genetic defect.
The first SMA gene therapy, Novartis’ Zolgensma (onasemnogene abeparvovec-xioi), was approved by the U.S. Food and Drug Administration (FDA) in 2019 for the treatment of SMA patients younger than 2. With Itvisma’s FDA approval for patients 2 and older, gene therapy is now authorized for SMA patients of all ages in the U.S.
The new approval is “profoundly meaningful because it confirms the scientific feasibility of addressing the core genetic deficiency, the missing SMN1 gene, regardless of a patient’s age or disease stage,” Lek said. “Equally important, it sends a strong message of inclusion and commitment to all individuals with SMA, such as the adults, who may have felt excluded from early gene therapy breakthroughs, and validates their right to access transformative therapies.”
Lek said Itvisma’s approval “is both a scientific milestone and a community milestone,” adding that “the SMA community’s strength — advocacy, participation in trials, and unwavering partnership — has been essential to every advance we see today.”
Trial showed therapy significantly improved motor function
The FDA’s approval of Itvisma was based mainly on data from two Phase 3 clinical trials. One study, STEER (NCT05089656), compared Itvisma against a sham procedure in kids and teens with SMA, with results showing that the gene therapy significantly improved motor function.
The other trial, dubbed STRENGTH (NCT05386680), tracked outcomes in 27 SMA patients who had been taking other SMA therapies before switching to Itvisma in the trial. Results showed patients had overall stable motor function after switching to one-time gene therapy. Findings from STRENGTH were recently published in Nature Medicine, in a Novartis-funded study, titled “Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial.”
“There is variability in change for individual participants, but overall stabilization was demonstrated as a group,” the researchers wrote in the paper.
The most common side effects of Itvisma include respiratory infections, digestive upset, fever, and headache. The therapy’s prescribing information also carries a boxed warning — the FDA’s most stringent safety warning — noting a risk of serious liver damage, which has been reported as a risk with Itvisma and Zolgensma, as well as other gene therapies for different diseases.
“The presence of the boxed warnings regarding risks like serious liver injury underscores the truth that these are novel, high-reward, high-risk interventions that demand exceptional vigilance and transparency,” Lek said. She added that patients need to have detailed discussions with their clinicians so they understand the specific risks in their situation, as well as steps that can be taken to mitigate those risks, but the decision about whether or not to pursue gene therapy ultimately “must be rooted in patient knowledge and shared decision-making with their clinical provider.”
Itvisma injected directly into spinal fluid
A key difference between Zolgensma and Itvisma is how they are administered. While Zolgensma is administered intravenously, or into the vein, Itvisma is given by intrathecal injection directly into the spinal fluid.
“Technically, the core advantage of [intrathecal] delivery is simple yet critical,” Lek said. “It allows the treatment to be directly administered to motor neurons in the spine, completely bypassing the general bloodstream and protective barriers of the brain. This direct delivery enables the use of a much smaller, safer dose of gene therapy.”
Conversely, limitations of intrathecal delivery include difficulties in evenly distributing the therapy to the entire brain and reaching muscles, Lek added.
This expanded landscape shifts care from passively awaiting progress to actively collaborating with patients to optimize functional outcomes and quality of life.
Although Itvisma is the first one-time gene therapy approved for older SMA patients, it isn’t the first disease-modifying therapy for this population: the injection therapy Spinraza (nusinersen) and the oral medication Evrysdi (risdiplam) are FDA-approved for SMA patients of all ages. The availability of a new option means that older SMA patients will be facing a “critical conversation” about continuing, switching, or combining treatments, Lek said.
“Every person living with SMA has a unique medical history, so decisions about switching or combining treatments should always be made with a neuromuscular specialist,” Lek said. “Important factors include treatment goals, prior response to therapy, safety considerations, and insurance coverage. Patients and their clinicians can strategically weigh different mechanisms, such as genetic intervention versus protein modulation, and different treatment commitments like one-time to continuous therapy. This expanded landscape shifts care from passively awaiting progress to actively collaborating with patients to optimize functional outcomes and quality of life.”
She noted that there is insufficient data on the safety or efficacy of combining these treatments, and scientists are continuing to learn more about how best to deploy gene therapies in SMA and neuromuscular diseases more broadly.
“Until more long-term data emerge, individualized and clinician-guided decision-making remains essential,” Lek said.
MDA offers variety of patient resources
Lek pointed to several resources offered by the MDA that may help patients navigate discussions about the benefits and risks of Itvisma. These include specialists at centers within the MDA Care Center Network, one-on-one support via the MDA Resource Center, and the MDA Gene Therapy Support Network, which is a dedicated resource for patients and clinicians investigating gene therapy access.
The MDA is also engaged in advocacy aimed at making Itvisma and other gene therapies more accessible for patients. In particular, issues with insurance coverage and the high cost of gene therapy can be major obstacles to access. Both Zolgensma and Itvisma carry list prices north of $2 million for the one-time treatment.
“The biggest [obstacle] to accessing gene therapies like Itvisima is the fundamental mismatch between the high, one-time cost of gene therapy and the current insurance system’s payment models. This financial dynamic creates complex bureaucratic and emotional barriers for families attempting to meet restrictive prior authorization criteria,” Lek said, noting that logistical issues, including center capacity and the small number of clinicians with expertise in SMA, can also make accessing care challenging.
“The MDA looks to address these gaps through MDA advocacy, whose priority is to help champion systemic solutions to secure greater access to these treatments while mitigating payer risk,” Lek added.
In addition to advocating for access to these cutting-edge treatments, the MDA is also working to advance research, building off breakthroughs in SMA to make gene therapy a reality for people with a wide range of other neuromuscular diseases.
“Strategically and compassionately, our core organizational goals are to leverage the resources and knowledge gained from these major breakthroughs to actively support and de-risk translational science across all the ultra-rare [neuromuscular diseases] we support. This approach ensures that we are helping to ensure the promise of gene therapy for every person in the neuromuscular community,” Lek said. “Accelerating gene therapy is central to MDA’s mission. We invest across the entire development pipeline — from basic science and early discovery through clinical trials and access advocacy.”
Lek also noted that the 2026 MDA Clinical & Scientific Conference will be held March 8 to 11, with attendance possible either virtually or in person in Orlando, Florida. She encouraged families interested in attending to fill out an online form, adding that discounted or free attendance is available for some patients, caregivers, and MDA volunteers.
The post Itvisma approval ushers in era of therapeutic choice for SMA patients appeared first on SMA News Today.
