Itvisma

Itvisma (onasemnogene abeparvovec) is a gene replacement therapy used for the treatment of SMA (spinal muscular atrophy) in adults and pediatric patients 2 years and older, with a confirmed mutation in the SMN1 gene. Itvisma helps improve motor function in patients with a confirmed mutation in the survival motor neuron 1 (SMN1) gene.

Itvisma works by delivering a functional SMN1 gene, allowing the body to produce effective SMN protein needed for motor neuron survival. Itvisma addresses the root cause of SMA by restoring the production SMN protein to slow further disease progression.

Itvisma is administered as a single-dose intrathecal injection.

Itvisma's FDA approval was granted for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with a confirmed mutation in the SMN1 gene, on November 24, 2025.

Itvisma demonstrated a statistically significant improvement in motor function for SMA patients in the STEER study, when compared to the placebo group.The phase 3 STEER study (NCT05089656) studied the effect of Itvisma vs placebo on motor function in children with spinal muscular atrophy (SMA), using the change in Hammersmith Functional Motor Scale–Expanded (HFMSE) score after 52 weeks. Enrolled SMA patients were 2 to 17 years old, treatment-naïve, and were able to sit but never able to walk independently.

The HFMSE score measures 33 motor tasks (e.g., sitting, standing, stair climbing) and ranges from 0–66. A higher HFMSE score = better motor function.

Clinical trial results

• Ivtsma patients +2.90 improvement in HFMSE score

• Placebo patients 0.51 increase in HFMSE score

• Treatment difference (ITVISMA –placebo): 1.88 points

• Patients treated with Ivtisma showed a 1.88-point greater improvement in motor function compared with those who received a placebo.

Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations or deletions in the SMN1 gene, which is essential for producing survival motor neuron (SMN) protein, a protein required for the survival of motor neurons.

Without the SMN protein, there is irreversible and progressive motor neuron loss, which leads to motor neurons degenerating, muscle wasting and weakness, and may include paralysis and death for severe cases.

Itvisma provides a functional gene that the body can use to create SMN protein, which protects the motor neurons and slows disease progression.

Itvisma and Zolgensma contain the same active ingredient (onasemnogene abeparvovec) but are formulated at different concentrations, delivered by different routes, and have different treatment groups.

Itvisma is a concentrated formulation administered directly to the central nervous system through a single intrathecal injection. The Itvisma dose is independent of patient weight, making it an option available to SMA patients older than 2 years of age.

Zolgensma is administered intravenously based on patient weight to pediatric patients less than 2 years of age.

Both treatments are developed and marketed by Novartis.

Itvisma's mechanism of action is a non-replicating recombinant AAV vector that delivers a functional copy of the human survival motor neuron 1 gene (SMN1), which results in continuous and sustained SMN expression in motor neurons.

Prophylaxis against influenza and RSV is recommended, and vaccination status should be up-to-date before Itvisma administration

Patients and caregivers should be aware that an infection, such as a cold, flu, gastroenteritis, otitis media, bronchiolitis, before or after Itvisma injection, could lead to more serious complications.

Pregnancy

Tell your health care provider if you are pregnant, planning a pregnancy, or become pregnant.

• There are no clinical studies in pregnant women to inform the associated risk with this product.
• There are no available data in animal embryo-fetal development studies with Itvisma.
• It is not known whether Itvisma has the potential to be transferred to the fetus.
• Therefore, women who are pregnant or desire to become pregnant should only be treated with ITVISMA after a thorough benefit-risk evaluation.

Breastfeeding

Tell your health care provider if you are breastfeeding or planning to breastfeed.

• There is no information available on the presence of this medicine in human milk, the effects on the breastfed infant, or the effects on milk production.
• The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Itvisma and any potential adverse effects on the breastfed child from this medicine or from the underlying maternal condition.

Females and Males of Reproductive Potential

Pregnancy Testing: Females of reproductive potential should have a verified negative pregnancy test before treatment with this medicine.

Females: Females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) and should refrain from egg donation for 6 months following ITVISMA administration.

Males: Men capable of fathering a child should use a barrier method of contraception and should refrain from sperm donation for 3 months following Itvisma administration.

The most common Itvisma side effects are upper respiratory tract infection, upper gastrointestinal symptoms, fever, and headache. These side effects occurred in at least 10% of patients in clinical trials.

Itvsma has a boxed warning for serious liver injury

Acute serious liver injury and elevated aminotransferases can occur with this medicine. Patients who have preexisting liver impairment or acute hepatic viral infection may be at higher risk of liver injury. Before your intrathecal injection, you will have your liver function assessed by clinical examination and laboratory testing. Systemic corticosteroid should be administered before and after Itvisma injection. Liver function should be monitored for at least 3 months after injection, and at other times as clinically indicated.

Other Warnings, Precautions, and Serious Side Effects

Liver Safety (hepatotoxicity): Your doctor will check your liver function with blood tests and an examination starting before you receive this medicine, during treatment, and for at least 3 months afterward, and longer if needed.

Low Platelet Counts (thrombocytopenia): Your platelet levels (which help your blood clot) will be checked before your injection, then at least once a week for the first month. Monitoring will continue until your levels return to normal.

Nerve Symptoms (peripheral sensory neuropathy): If you develop numbness, tingling, or other nerve-related symptoms, your doctor may order neurological tests or provide treatments to help manage them.

Blood Vessel and Organ Damage (Thrombotic Microangiopathy - TMA): Watch for symptoms such as unusual bruising, swelling, decreased urination, or extreme fatigue. These can be serious. If any signs appear, your doctor will involve specialists right away.

Heart Monitoring (Elevated Cardiac Troponin I): Some people have had increases in cardiac troponin I (a heart muscle protein) after receiving Itvisma. Your doctor may check your heart and consult a heart specialist if needed.

Very Rare Risk of Tumor Formation: There is a theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome. Report cases of tumors in patients who received Itvisma to Novartis Gene Therapies, Inc.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088

Itvisma is administered as an intrathecal injection over approximately 1 to 2 minutes through the lumbar puncture needle.

You will receive corticosteroid medicine before and after your injection.

Patient’s vaccination schedule should be adjusted to accommodate concomitant corticosteroid administration prior to and following Itvisma injection

Certain vaccines, such as measles, mumps, and rubella (MMR) and varicella, are contraindicated for patients on a substantially immunosuppressive steroid dose (i.e., ≥ 2 weeks of daily receipt of 20 mg or 2 mg/kg body weight of prednisone or equivalent).

Novartis Gene Therapies, Inc. 2275 Half Day Road Bannockburn, IL 60015 USA