Spinal Muscular Atrophy (SMA) Treatments

ITVISMA is indicated for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in

ITVISMA is a clear to slightly opaque, colorless to faint white suspension for intrathecal injection.

Each single-dose vial contains 1.2 × 10

ITVISMA has a nominal concentration of 4 × 10

None.

Adjust patient’s vaccination schedule to accommodate concomitant corticosteroid administration prior to and following ITVISMA injection

ITVISMA (onasemnogene abeparvovec-brve) is a suspension of an adeno-associated viral vector-based gene therapy for intrathecal injection. It is a recombinant self-complementary AAV9 containing a transgene encoding the human survival motor neuron (SMN) protein, under the control of a cytomegalovirus enhancer/chickenβactin hybrid promoter.

ITVISMA has a nominal concentration of 4 × 10

The efficacy of ITVISMA was evaluated in a randomized, double-blind, sham-controlled study (Study 1; NCT05089656). The study enrolled patients with spinal muscular atrophy (SMA) who were treatment-naive, and able to sit but never able to walk independently. Patients with elevated (reference to > 1:50) baseline serum anti-AAV9 antibody titer were excluded.

A total of 136 patients were randomized in 3:2 ratio to receive either ITVISMA at a dose of 1.2 x 10

The demographic characteristics of the population were as follows: the mean age was 6 years (range 2 to 17 years), 62 patients (49%) were male, 74 patients (59%) were Asian, 14 patients (11%) were White, 9 patients (7%) were Black or African American, and 7 patients (6%) were American Indian or Alaska Native, 22 patients (18%) were of “unknown” race. One hundred and twenty-two patients (97%) had confirmed biallelic deletion (0 copies) of the

The primary endpoint was the change from baseline in HFMSE total score at the end of follow-up, defined as the average of the Week 48 and Week 52 assessment, in ITVISMA compared to sham. The HFMSE evaluates motor function in patients with SMA who have limited ambulation, comprising of 33 graded items that assess various motor skills ranging from sitting to using the stairs. Each item is scored from 0-2, with a maximum total score of 66. Higher scores indicate better motor function.

The efficacy results from Study 1 are summarized in Table 4 below.

Inform patients and caregivers that ITVISMA could increase liver enzyme levels. Inform patients and caregivers that patients will receive an oral corticosteroid medication before and after ITVISMA injection, and will undergo regular blood tests to monitor liver function. Advise patients and caregivers to contact their healthcare provider immediately if the patient’s skin and/or whites of the eyes appear yellowish, if the patient misses a dose of corticosteroid or vomits it up, or if the patient experiences a decrease in alertness

Advise patients and caregivers to consult with their healthcare provider to determine if adjustments to the patient’s vaccination schedule are necessary during corticosteroid use. Inform patients and caregivers that where feasible, the vaccination schedule should be adjusted appropriately to accommodate treatment with corticosteroid. Prophylaxis against influenza and RSV is recommended and vaccination status should be up-to-date prior to ITVISMA administration. Please consult your health care provider

Patients and caregivers should be aware that an infection (e.g., cold, flu, gastroenteritis, otitis media, bronchiolitis, etc.) before or after ITVISMA injection could lead to more serious complications. Patients, caregivers and close contacts of patients should follow infection prevention practices (e.g., hand hygiene, coughing/sneezing etiquette, limiting potential contacts). Advise patients and caregivers of the signs of a possible infection, such as coughing, wheezing, sneezing, runny nose, sore throat, or fever. Patients and caregivers should contact their healthcare provider immediately if the patient experiences any symptoms suggestive of infection before or after ITVISMA injection

Inform patients and caregivers that ITVISMA could decrease blood platelet count and increase the risk of bruising or bleeding. Inform patients and caregivers that decreases in platelet counts were observed within the first week after ITVISMA injection. Advise patients and caregivers to seek medical attention if the patient experiences unexpected bruising or bleeding

Inform patients and caregivers that peripheral sensory neuropathy has occurred with ITVISMA administration. Advise patients and caregivers to contact their healthcare provider promptly if the patient experiences numbness, tingling, prickling, or pain in the arms, hands, legs and/or feet

Inform patients and/or caregivers that decreased blood platelet and red blood cell counts, acute kidney injury, and increased bruising or bleeding, which may be indicative of TMA, can occur. Advise patients and/or caregivers to seek immediate medical attention if the patient experiences unexpected bruising or bleeding, seizures, or decreased urine output

Inform patients and/or caregivers that there is a theoretical risk of tumorigenicity with AAV therapies such as ITVISMA. Advise patients and/or caregivers to contact their healthcare provider and Novartis Gene Therapies, Inc. (1-833-828-3947) if the patient who received ITVISMA develops a tumor

Advise women of childbearing potential to use an effective method of contraception and to refrain from egg donation for 6 months following ITVISMA injection. Advise men capable of fathering a child to use a barrier method of contraception and to refrain from sperm donation for 3 months following ITVISMA injection

Manufactured by, Packed by, Distributed by:

Novartis Gene Therapies, Inc.

2275 Half Day Road

Bannockburn, IL 60015 USA

U.S. License Number 2250

©2025 Novartis Gene Therapies, Inc.

T2025-67

NDC 71894-200-02

Rx only

onasemnogene

itvisma

1.2 × 10

(4 x 10

Sterile solution for Intrathecal Injection Only

One Single-dose Vial

Must use within 14 days of receipt

DO NOT SHAKE | DO NOT REFREEZE

NOVARTIS