ITVISMA UAE

Regulatory Affairs

Itvisma^TM (onasemnogene abeparvovec) 

3 mL Solution for intrathecal injection

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Itvisma^TM

Important note: Before prescribing, consult full prescribing information: https://www.fda.gov/.

Disclaimer: This link will contain the most updated product information approved by the reference country.

Presentation:

Solution for intrathecal injection: Each single-dose vial contains 1.2 × 10¹⁴ vector genomes (vg) of onasemnogene abeparvovec in 3 mL of solution.

Indications:

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 survival motor neuron 1 (SMN1) gene.

Dosage and administration:

Critical Dosing Information

For single-dose intrathecal injection only.

• Patients previously treated with ZOLGENSMA (onasemnogene abeparvovec-xioi) should not be treated with ITVISMA [see Clinical Pharmacology (12.1)].
• ITVISMA should only be administered intrathecally using a lumbar puncture by healthcare professionals (e.g., interventional radiologist or neurologist) experienced in performing lumbar punctures.
• Prior to ITVISMA injection:
  • Due to the increased risk of serious systemic immune response, administer ITVISMA to patients who are clinically stable in their overall baseline health status (e.g., hydration and nutritional status, absence of infection, respiratory status) prior to administration. Postpone ITVISMA in patients with active or recent infections, until the infection has resolved, and the patient is clinically stable. Clinical signs or symptoms of infection should not be evident at the time of ITVISMA injection.
  • Assess vaccination status. Vaccination status should be up-to-date prior to ITVISMA administration. Recommend seasonal prophylaxis against respiratory syncytial virus (RSV).
  • Assess liver function (clinical examination and laboratory testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, prothrombin time, partial thromboplastin time (PTT), international normalized ratio (INR), and total bilirubin) [see Warnings and Precautions (5.1), Use in Specific Populations (8.6)].
  • Obtain creatinine and complete blood count (including hemoglobin and platelet count) [see Warnings and Precautions (5.2, 5.4)].
  • Perform baseline testing for the presence of anti-AAV9 antibodies.
• One day prior to ITVISMA injection, begin administration of systemic corticosteroids equivalent to oral prednisolone at 1 mg per kg of body weight per day (mg/kg/day) for a total of 30 days. Do not stop systemic corticosteroids abruptly. After the 30-day period, taper prednisolone (or equivalent) as needed according to the clinical status and liver function testing [see Warnings and Precautions (5.1, 5.2)]. See Table 1 for the recommended corticosteroid regimen.
• Do not re-administer ITVISMA.

Dose

The recommended dose of ITVISMA is 1.2 × 10¹⁴ vector genomes (vg).

Table 1 includes the recommended corticosteroid regimen prior to and following ITVISMA injection.

If at any time patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone, based on the patient’s clinical course, obtain prompt consultation with a gastroenterologist or hepatologist and consider adjustment to the recommended corticosteroid regimen, including increased dose, longer duration or prolongation of corticosteroid taper [see Warnings and Precautions (5.1)]. If oral corticosteroid therapy is not tolerated or not effective, consider intravenous corticosteroids, as clinically indicated.

Table 1:           Recommended Corticosteroid Regimen Pre- and Post- ITVISMA Injection

Preparation

Required supplies and materials (not supplied)

• Needle for withdrawal
• Syringe
• Syringe cap
• Spinal needle

The supplies and materials compatible with ITVISMA are listed in Table 2. Device components must be indicated for intrathecal or neuraxial use. Ensure all device components use the same connector type. Incompatible device connections may result in dose loss during administration.

Table 2:           Component Materials Compatible With ITVISMA

^a Not to be manufactured with Polyvinylchloride (PVC), Bisphenol-A (BPA), Bis(2- ethylhexyl) phthalate (DEHP) or Latex

Vial Preparation:

• ITVISMA should be prepared aseptically.
• Thaw ITVISMA in the refrigerator for approximately 4 hours, or at room temperature for approximately 1 hour. If thawed in the refrigerator, remove ITVISMA from refrigerator on day of dosing.
• Do not use ITVISMA unless thawed.
• Prior to intrathecal injection, ITVISMA should be brought to room temperature.
• When thawed, ITVISMA is a clear to slightly opaque, colorless to faint white solution, free of particles. After withdrawal of ITVISMA from the vial, a visual inspection is required. DO NOT use if particulates, cloudiness, or discoloration are visible.
• DO NOT SHAKE.
• Immediately prior to dosing, draw the content from the vial into the syringe, remove air from syringe, confirm the dose volume of 3 mL in the syringe, cap syringe and deliver to patient injection location.
• Once dose is drawn into the syringe, it may be held in the refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours, including a 5-hour maximum time out-of-refrigeration allowance within the 24-hour period. Discard the vector-containing syringe if not injected within this time period.
• DO NOT REFREEZE.

Procedural Preparation Instructions:

• Consider sedation if indicated by the patient’s clinical status.
• Consider imaging techniques to guide intrathecal injection of ITVISMA.
• Evaluate patient prior to and after intrathecal injection for conditions that may contraindicate lumbar puncture or increase procedural risk to prevent serious complications.

Administration

Intrathecal Injection Instructions:

• Prior to administration, remove 3 mL of cerebrospinal fluid (CSF) using a lumbar puncture needle to create space for injection volume.
• Administer ITVISMA as an intrathecal bolus injection over approximately 1 to 2 minutes through the lumbar puncture needle.
• Place patient in Trendelenburg position (head down at 30 degrees for 15 minutes). Adjust patient positioning and duration based on the patient’s clinical status to enhance distribution.
• Follow standard post-lumbar puncture care protocols. 

Monitoring Following ITVISMA Injection:

• Liver function (AST, ALT, total bilirubin) weekly for the month after ITVISMA injection and during the corticosteroid taper period (over the next 28 days or longer if needed). If the patient is clinically stable with unremarkable findings (normal clinical exam, total bilirubin, and ALT and AST levels below 2 × ULN) at the end of the corticosteroid taper period, continue to monitor liver function every other week for another month [see Warnings and Precautions (5.1)].
• Platelet counts weekly for the first month and as clinically indicated until platelet counts return to baseline [see Warnings and Precautions (5.2)].

Contraindications:

None.

Warnings and precautions:

• Hepatotoxicity: Hepatotoxicity, which generally manifested as elevated ALT and/or AST levels, has occurred with Itvisma. Patients with pre-existing hepatic impairment or acute hepatic viral infection may be at higher risk of liver injury. A systemic corticosteroid should be administered to all patients before and after Itvisma injection. Liver function should be assessed prior to injection and monitored for at least 3 months after injection, and at other times as clinically indicated. Promptly assess and closely monitor patients with worsening liver function test results and/or signs or symptoms of acute illness. In case hepatic injury is suspected, further testing is recommended (e.g., albumin, prothrombin time, partial thromboplastin time (PTT) and international normalized ratio (INR)). ♦Thrombocytopenia: Platelet counts should be obtained before Itvisma injection and should be monitored on a regular basis afterwards; at least weekly for the first month and as clinically indicated until platelet counts return to baseline. ♦Peripheral sensory neuropathy: Administration of Itvisma may result in sensory symptoms (e.g., numbness, tingling, prickling, or pain in the arms, hands, legs and/or feet). Complete neurological evaluation and other testing and/or symptom management should be considered based on the patient’s clinical presentation. ♦Thrombotic microangiopathy (TMA): Prompt attention to signs and symptoms of TMA is advised, as TMA can result in life-threatening or fatal outcomes. If clinical signs, symptoms and/or laboratory findings occur, a hematologist and/or nephrologist should be consulted immediately to manage TMA as clinically indicated. ♦Theoretical risk of tumorigenicity as a result of vector integration: There is a theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome.

Pregnancy, lactation, females and males of reproductive potential

Pregnancy: There are no adequate and well-controlled studies in pregnant women to inform a product- associated risk. Animal reproduction studies in mice have shown no risk of fetal abnormalities nor transfer to mouse fetus. Women who are pregnant or may become pregnant should be treated with Itvisma after a thorough benefit-risk evaluation.

Lactation: There is no information available on the presence of Itvisma in human milk, the effects on the breastfed infant or the effects on milk production.

Fertility: There is no data on the effect of ITVISMA on human fertility. In animal fertility studies, onasemnogene abeparvovec did not impact fertility in male and female mice at a dose of 1.1 × 10¹⁴ vg/kg administered intravenously.

Adverse drug reactions:

Very common (≥10%): Upper respiratory tract infection, headache, vomiting, pyrexia

Common (≥1 to <10%): Thrombocytopenia, dizziness, sensory disturbance, pain in extremity, hepatic enzyme increased