ITVISMA Solution for injection Ref.[116806] Active ingredients: Onasemnogene abeparvovec

Treatment should be initiated and administered in clinical centres and supervised by a physician experienced in the management of patients with SMA.

Before administration of Itvisma, baseline laboratory testing is required, including, but not limited to:

• AAV9 antibody testing using an appropriately validated assay (see section 4.4),
• liver function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (see section 4.4),
• creatinine, and
• complete blood count (including haemoglobin and platelet count) (see section 4.4).

It is recommended that patients are clinically stable in their overall health status prior to injection (see section 4.4). The benefit-risk profile of Itvisma in patients with respiratory failure, on permanent ventilation, and/or unable to swallow is not established.

Because the treatment persists in non-dividing cells, patients previously treated with onasemnogene abeparvovec (any route of administration) should not be treated with Itvisma (see section 5.1).

Posology

Itvisma is administered as a single dose of 1.2 × 10¹⁴ vg.

Immunomodulatory regimen

To dampen an immune response, immunomodulation with corticosteroids is recommended. Elevations in liver aminotransferases or decreased platelet counts may occur following treatment (see sections 4.4 and 4.8). Where feasible, the patient's vaccination schedule should be adjusted to accommodate concomitant corticosteroid administration prior to and following Itvisma injection (see section 4.5).

Table 1 shows the recommended immunomodulatory regimen prior to and following injection.

Table 1. Recommended immunomodulatory regimen pre- and post-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, prompt consultation with a gastroenterologist or hepatologist and adjustment to the recommended immunomodulatory regimen, including increased dose, longer duration or prolongation of corticosteroid taper, may be considered (see section 4.4). If oral corticosteroid therapy is not tolerated or not effective, intravenous corticosteroids may be considered as clinically indicated.

If another corticosteroid is used by the physician in place of prednisolone, similar considerations and approach to taper the corticosteroid dose after 30 days should be taken as appropriate.

Special populations

Renal impairment

The safety and efficacy of Itvisma have not been established in patients with renal impairment. A dose adjustment should not be considered.

Hepatic impairment

Itvisma therapy should be carefully considered in patients with hepatic impairment (see section 4.4). A dose adjustment should not be considered.

Paediatric population

The safety and efficacy of Itvisma in children aged under 2 years have not been established. Currently available data are described in sections 4.8 and 5.1 but no recommendation on a posology can be made in children aged 6 months to ˂2 years. No data are available in children aged ˂6 months.

Adult population

No clinical study data are available in patients aged 18 years and older.

Method of administration

For intrathecal use. Treatment should be administered intrathecally using a lumbar puncture by healthcare professionals experienced in performing lumbar punctures.

• Immediately prior to dosing, draw the content from the vial into the syringe, remove air from the syringe, confirm the dose volume of 3 mL in the syringe, cap the syringe and deliver to the patient injection location.
• If indicated by the patient's clinical status, sedation should be considered.
• Imaging techniques to guide intrathecal injection may be considered.
• The patient should be evaluated prior to and after intrathecal injection for the presence of potential conditions related to lumbar puncture, to avoid serious procedural complications.
• Prior to administration, remove 3 mL of cerebrospinal fluid (CSF) using a lumbar puncture needle.
• Itvisma is administered as a single-dose bolus intrathecal injection over approximately 1 to 2 minutes.
• Following intrathecal injection, placement in Trendelenburg position (depending on the patient's clinical status) is recommended.

For detailed instructions on the preparation, handling, accidental exposure and disposal of the medicinal product, see section 6.6.

No data from clinical studies are available regarding overdose of Itvisma. The dose of Itvisma is a single, fixed dose and is administered only once, therefore overdose is considered unlikely.

2 years.

After thawing:

Once thawed, the medicinal product should not be re-frozen.

May be stored refrigerated at 2°C to 8°C in the original carton for 14 days. The date of receipt should be marked on the original carton before the medicinal product is stored in the refrigerator.

Once the dose is drawn into the syringe, it may be held at 2°C to 8°C for up to 24 hours, including a 5-hour maximum time out-of-refrigeration allowance within the 24-hour period. The vector-containing syringe should be discarded if not used within this time period.

Store and transport frozen (≤ -60°C).

Store in a refrigerator (2°C – 8°C) immediately upon receipt.

Store in the original carton.

For storage conditions after thawing of the medicinal product, see section 6.3.

Itvisma is supplied in a single-dose clear vial (5 mL cyclic olefin polymer) with stopper (20 mm chlorobutyl rubber) and seal (aluminium, flip-off) with a coloured cap (plastic). Each vial has a fill volume of 3 mL.

Each carton contains 1 vial.

Thawing:

• Thaw Itvisma in the refrigerator (2°C to 8°C) for approximately 4 hours, or at room temperature (20°C to 25°C) for approximately 1 hour.
• Prior to intrathecal injection, Itvisma should be brought to room temperature.
• Itvisma is a clear to slightly opaque, colourless to faint white solution. Do not use this medicinal product if you notice any particles, cloudiness, or discolouration once the frozen product has thawed and prior to administration.
• Do not shake.
• Once thawed, the medicinal product should not be re-frozen.
• After thawing, Itvisma should be given as soon as possible. Once the dose volume is drawn into the syringe it may be held in the refrigerator (2°C to 8°C) 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 used within this time period.

Precautions to be taken before handling or administering the medicinal product:

• Itvisma should be handled aseptically under sterile conditions.
• This medicinal product contains genetically modified organisms (GMOs).
• Personal protective equipment (including gloves, safety goggles, laboratory coat and sleeves) should be worn while handling or administering Itvisma.
• The vial must be thawed before use. Do not use Itvisma unless thawed.
• Immediately prior to dosing, draw the content from the vial into the syringe, remove air from the syringe, confirm the dose volume of 3 mL in the syringe, cap the syringe and deliver to the patient injection location.
• When assembling the injection, it must be ensured that the components' surface in contact with Itvisma solution consists of the compatible materials listed in Table 4. Device components must be indicated for intrathecal or neuraxial use.

Table 4. Component materials compatible with Itvisma:

^a Not to be manufactured with polyvinylchloride (PVC), bisphenol-A (BPA), bis(2-ethylhexyl) phthalate (DEHP) or latex

Precautions to be taken for the disposal and accidental exposure to the medicinal product:

• All spills of Itvisma must be wiped with absorbent gauze pad and the spill area must be disinfected using a bleach solution followed by alcohol wipes. All clean up materials must be double bagged and disposed of in accordance with local guidelines for handling of biological waste.
• Any unused medicinal product or waste material should be disposed of in accordance with local guidelines on handling of biological waste.
• All materials that may have come in contact with Itvisma (e.g. vial, all materials used for injection, including sterile drapes and needles) must be disposed of in accordance with local guidelines on handling of biological waste.
• Accidental exposure to Itvisma must be avoided. In the event of accidental exposure to skin, the affected area must be thoroughly cleaned with soap and water for at least 15 minutes. In the event of accidental exposure to eyes, the affected area must be thoroughly flushed with water for at least 15 minutes.