ITVISMA

2 DOSAGE AND ADMINISTRATION For single-dose intrathecal injection only. ( 2 ) The recommended dose of ITVISMA is 1.2 × 10 14 vector genomes (vg). ( 2.2 ) Administer ITVISMA as an intrathecal bolus injection over approximately 1 to 2 minutes. ( 2.4 ) Postpone ITVISMA in patients with infections until the infection has resolved and the patient is clinically stable. ( 2.1 ) Starting one day prior to ITVISMA injection, administer systemic corticosteroids equivalent to oral prednisolone at 1 mg/kg of body weight per day for a total of 30 days. At the end of the 30-day period, check liver function by clinical examination and by laboratory testing. For patients with unremarkable findings, taper the corticosteroid dose gradually over the next 28 days. If liver function abnormalities persist, continue systemic corticosteroids (equivalent to oral prednisolone at 1 mg/kg/day) until findings become unremarkable, and then taper the corticosteroid dose gradually over the next 28 days or longer if needed. Do not stop systemic corticosteroids abruptly. ( 2.2 ) 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, prompt consultation with a gastroenterologist or hepatologist and adjustment to the recommended corticosteroid regimen may be considered. ( 2.2 ) 2.1 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. 2.2 Dose The recommended dose of ITVISMA is 1.2 × 10 14 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 Pre-Injection - 24 hours prior to ITVISMA injection Oral prednisolone 1 mg/kg/day (or equivalent) Post-Injection - 30 days (including the day of ITVISMA administration) Oral prednisolone 1 mg/kg/day (or equivalent) Followed by 28 days: For patients with unremarkable findings (normal clinical exam, total bilirubin, and ALT and AST levels below 2 × ULN) or For patients with liver function abnormalities at the end of the 30 day period: continue until the AST and ALT values are both below 2 × ULN and all other assessments return to normal range, and then taper the corticosteroid dose over the next 28 days or longer if needed . Systemic corticosteroids should be tapered gradually Taper prednisolone (or equivalent) Systemic corticosteroids (equivalent to oral prednisolone 1 mg/kg/day) Systemic corticosteroids should be tapered gradually 2.3 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 Component Material of Construction 18G to 19G Needle for withdrawal, maximum 1.5” long Stainless steel 5mL to 10mL Syringe a Polypropylene Syringe cap a Polypropylene or Polyethylene or Methacrylate-Acrylonitrile-Butadiene-Styrene 22G to 27G Spinal needle, maximum 150mm long Stainless steel 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 liquid, 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. 2.4 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)] .

See official label

1 INDICATIONS AND USAGE 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.