Novartis exec: Itvisma approval ‘important moment’ for community
FDA nod makes 'transformative' gene therapy available to all
- FDA approved Itvisma, a one-time gene therapy for SMA patients ages 2 and older.
- Itvisma restores SMN protein, improving motor function and reducing treatment burden.
- A Novartis executive says the approval is an 'important moment' for the SMA community.
Last week’s U.S. Food and Drug Administration (FDA) approval of Novartis‘ gene therapy Itvisma (onasemnogene abeparvovec-brve) means the one-time gene therapy is now authorized for all people with spinal muscular atrophy (SMA) in the U.S., an “important moment” for the SMA community, said Tracey Dawson, PhD, senior vice president and U.S. therapeutic area head of neuroscience at the company.
“We believe everyone with SMA deserves the chance to benefit from a transformative treatment — no matter their age, and no matter how severe their disease is,” Dawson said in a written Q&A with SMA News Today. “For the first time, gene replacement therapy is an option for people with SMA of all ages.”
The FDA approved Itvisma to treat SMA patients ages 2 and older. Zolgensma (onasemnogene abeparvovec-xioi), another SMA gene therapy sold by Novartis, has been FDA-approved for SMA patients up to age 2 since 2019.
“Every day, we are driven by the more than 5,000 patients lives we’ve touched with Zolgensma,” Dawson said. “Now with Itvisma, we are able to offer one-time gene therapy to patients of all ages with SMA, address critical unmet needs for an even broader SMA population. This is what inspires us to continue in our commitment to reimagining medicine and what’s possible for patients and their loved ones.”
Fixed dose delivered directly into CSF
SMA is caused primarily by mutations in the gene SMN1, leading to low levels of a protein called SMN. Low SMN levels cause motor neurons, the nerve cells that control movement, to sicken and die, ultimately leading to SMA symptoms such as progressive muscle weakness.
Both Itvisma and Zolgensma are designed to deliver a healthy version of the SMN1 gene to cells, thus restoring SMN protein production and stopping disease progression. While Zolgensma is delivered by infusion into the bloodstream, Itvisma is given directly into the fluid that surrounds the brain and spinal cord, known as cerebrospinal fluid (CSF), via intrathecal injection into the spinal canal. Since the amount of CSF in the body stays relatively constant from age 2 on, this allows a set dose of Itvisma to be used in patients of all ages and sizes.
“We believe the intrathecal administration of Itvisma provides a favorable risk-benefit profile for older children and young adults with SMA, given its fixed dosing that is delivered directly to the cerebrospinal fluid (CSF), irrespective of patient body weight and age,” Dawson said.
Dawson noted that Itvisma can be administered to patients with scoliosis (an abnormal sideways curvature of the spine), which is a common symptom of SMA. But “individual eligibility may vary,” she said, and “patients and families should speak with their physician to determine what’s right for them.”
FDA approval of Itvisma was based mainly on data from two Phase 3 clinical trials: STEER (NCT05089656), which showed that the therapy was better than a sham procedure at improving motor function, and STRENGTH (NCT05386680), which showed stable motor function scores in patients who switched to Itvisma from other SMA therapies.
“In the STEER study, treatment with Itvisma led to a 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE) – a gold standard for SMA-specific assessment of motor ability and disease progression and often used in clinical trials and natural history studies to assess functional changes,” Dawson said. “While this can mean different things for different severities of the disease, any motor function improvement or stabilization of disease for people with SMA can allow them the opportunity for more independence in daily activities.”
Novartis is continuing to run a trial called SPECTRUM (NCT05335876) that’s collecting long-term follow-up data on SMA patients who participated in clinical trials of Itvisma.
One-time treatment could reduce burden for patients
Itvisma is the third disease-modifying therapy to be approved in the U.S. for SMA patients older than 2, following Biogen‘s intrathecal therapy Spinraza (nusinersen) and Roche‘s oral medication Evrysdi (risdiplam). All these therapies are designed to boost SMN protein production, albeit through different mechanisms: Itvisma delivers a healthy copy of the SMN1 gene, and Spinraza and Evrysdi work by modulating the activity of another gene, SMN2.
And while Itvisma is a one-time treatment, Spinraza and Evrysdi are designed to be taken regularly over a patient’s entire lifetime. Itvisma offers “the potential to reduce the lifetime treatment burden associated with available therapies,” Dawson said.
Dawson noted that there are no formal studies directly comparing Itvisma against Spinraza or Evrysdi. There also haven’t been formal studies testing whether these therapies can provide additional benefits if combined, and Dawson said that Novartis currently has “no formal plans for a study evaluating the combination of Itvisma with other therapies.”
According to Itvisma’s prescribing information, the most common side effects of the treatment include upper respiratory tract infection, digestive upset, fever, and headache. The therapy also carries a boxed warning — the FDA’s most stringent safety warning — noting a risk of liver damage.
Dawson said that “liver-related events were low-grade across clinical studies of Itvisma,” but noted that serious liver damage may occur with similar gene therapies. Patients receiving Itvisma will receive pre-treatment testing to check vaccination status and organ health, and anti-inflammatory medications will be given before and after gene therapy to help reduce the risk of adverse reactions, she said.
“Individual experiences and considerations may vary, so we encourage patients to speak with their physicians about what may be right for them,” she said.
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