FDA approves SMA gene therapy Itvisma for patients 2 and older
By year's end, one-time treatment will be available to all ages in US
- FDA approved Itvisma, a gene therapy for SMA patients aged 2 and older.
- Itvisma delivers a healthy SMN1 gene via spinal injection in a one-time treatment.
- This expands gene therapy access to older children and adults with SMA.
Before the end of this year, thanks to a new decision by the U.S. Food and Drug Administration (FDA), one-time gene therapy will be available to people of all ages with spinal muscular atrophy (SMA) in the United States.
The first SMA gene therapy, Zolgensma (onasemnogene abeparvovec-xioi), was approved by the FDA in 2019 for children as old as 2 with the genetic condition. On Monday, the FDA approved a new gene therapy called Itvisma (onasemnogene abeparvovec-brve) for SMA patients ages 2 and older.
It will be the first gene therapy available to adults and older children, the FDA noted in an agency press release.
“Significant unmet need remains in SMA, particularly for patients across various ages and motor function levels, predominantly those 2 years of age and older,” said Vijay Kumar MD, acting director of the office of therapeutic products in the FDA’s Center for Biologics Evaluation and Research. “This approval shows our continued commitment to supporting and facilitating treatments for patients with rare diseases.”
According to Novartis, which owns both Zolgensma and Itvisma, the newly approved gene therapy is expected to be commercially available starting in December. The company offers a patient support program, available by phone at 855-441-4363, which can provide personalized help in understanding insurance coverage and finding financial assistance options.
“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,” Victor Bultó, president of Novartis U.S., said in a company press release. “We are proud to support the SMA community by empowering patients of all ages through our innovative, one-time therapies, offering the potential to reduce the burden that comes with chronic treatment.”
Novartis and Cure SMA are hosting a webinarat noon ET on Dec. 11 to share more information about the newly approved therapy with the U.S. SMA community. Registration is available online.
Typically a progressive disorder, SMA is mainly caused by mutations in the gene SMN1. In SMA, motor neurons — the nerve cells that control movement — sicken and die, leading to symptoms such as muscle weakness and wasting.
Itvisma given by single injection into spinal canal
Both Zolgensma and Itvisma contain the same gene therapy construct, called onasemnogene abeparvovec. This construct is basically a virus that’s been modified so that instead of causing an infection, it will deliver a healthy version of the SMN1 gene to nerve cells, thus addressing the root cause of SMA.
The key difference between Zolgensma and Itvisma is the route of administration: Zolgensma is given intravenously, by infusion into the bloodstream, while Itvisma is given by injection into the spinal canal, which is known as an intrathecal injection. Because the amount of fluid in the spinal cord remains relatively constant from age 2 on, this allows a single dose to be used in everyone from young children to adults. (The recommended dose of Itvisma is 1.2×1014 vector genomes.)
“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,” said Kenneth Hobby, president of Cure SMA, a nonprofit advocacy organization in the U.S.
“The SMA disease landscape has dramatically changed over the last six years, when the first gene therapy was approved. This is another welcome advancement, and it represents real progress in expanding access for many older patients and addressing the unmet needs that remain in our community,” Hobby said.
[This] approval shows the power of gene therapies and offers treatment to patients across the SMA disease spectrum, including patients at various ages, SMA symptoms, and motor functional levels.
The FDA’s approval of Itvisma was based mainly on two Phase 3 clinical trials that tested the gene therapy: STEER (NCT05089656) and STRENGTH (NCT05386680). Both enrolled children and teens, ages 2 to 17, with SMA.
STEER compared Itvisma against a sham procedure in patients who’d never previously been treated, and its results showed the therapy significantly improved motor function. STRENGTH, meanwhile, tested Itvisma in individuals who’d previously been on other therapies. The results of that trial showed patients had stable motor function after discontinuing previous therapies and receiving the one-time gene therapy.
“[This] approval shows the power of gene therapies and offers treatment to patients across the SMA disease spectrum, including patients at various ages, SMA symptoms, and motor functional levels,” said Vinay Prasad, MD, the FDA’s chief medical and scientific officer, and the director of the Center for Biologics Evaluation and Research.
“This exciting area of science continues to change the lives of patients and the FDA is committed to expediting the development of products for unmet medical needs,” Prasad added.
Itvisma had a consistent safety profile across the two clinical trials. The most common adverse reactions seen with the therapy have been upper respiratory tract infection, upper digestive symptoms, fever, and headache. Itvisma’s prescribing information carries a boxed warning, which is the FDA’s most stringent safety warning, noting that it can cause serious liver injury. A similar warning is noted in the prescribing information for Zolgensma.
Gene therapy’s approval cheered by patients, SMA advocates
The therapy’s approval was applauded by advocates and patients, with the Muscular Dystrophy Association heralding it as “a major step forward.”
“As someone living with spinal muscular atrophy, I’ve witnessed firsthand the incredible progress our community has made thanks to continued research and innovation,” Mindy Henderson, vice president of disability outreach and empowerment at the MDA, said in a press release from the association that noted that Itvisma is “the first and only gene replacement therapy available to [a] broader SMA population” including adults and teenagers.
“This approval represents not only scientific advancement but renewed hope for people and families living with SMA,” Henderson said. “It inspires a lot of hope in the SMA community to see how far we’ve come, and to know that organizations like the Muscular Dystrophy Association, together with our partners in science and industry, are helping to make what once felt impossible, possible.”
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