LUXTURNA Concentrate and solvent for solution for injection Ref.[8763] Active ingredients: Voretigene neparvovec

Treatment should be initiated and administered by a retinal surgeon experienced in performing macular surgery.

Posology

Patients will receive a single dose of 1.5 x 10¹¹ vector genomes voretigene neparvovec in each eye. Each dose will be delivered into the subretinal space in a total volume of 0.3 mL. The individual administration procedure to each eye is performed on separate days within a close interval, but no fewer than 6 days apart.

Immunomodulatory regimen

Prior to initiation of the immunomodulatory regimen and prior to administration of voretigene neparvovec, the patient must be checked for symptoms of active infectious disease of any nature, and in case of such infection the start of treatment must be postponed until after the patient has recovered.

Starting 3 days prior to the administration of voretigene neparvovec to the first eye, it is recommended that an immunomodulatory regimen is initiated following the schedule below (Table 1). Initiation of the immunomodulatory regimen for the second eye should follow the same schedule and supersede completion of the immunomodulatory regimen of the first eye.

Table 1. Pre- and post-operative immunomodulatory regimen for each eye:

Special populations

Elderly

The safety and efficacy of voretigene neparvovec in patients ≥65 years old have not been established. Data are limited. However, no adjustment in dose is necessary for elderly patients.

Hepatic and renal impairment

The safety and efficacy of voretigene neparvovec have not been established in patients with hepatic or renal impairment. No dose adjustment is required in these patients (see section 5.2).

Paediatric population

The safety and efficacy of voretigene neparvovec in children aged up to 4 years have not been established. Data are limited. No adjustment in dose is necessary for paediatric patients.

Method of administration

Subretinal use.

Luxturna is a sterile concentrate solution for subretinal injection that requires thawing and dilution prior to administration (see section 6.6).

This medicinal product must not be administered by intravitreal injection.

Luxturna is a single-use vial for a single administration in one eye only. The product is administered as a subretinal injection after vitrectomy in each eye. It should not be administered in the immediate vicinity of the fovea to maintain foveal integrity (see section 4.4).

The administration of voretigene neparvovec should be carried out in the surgical suite under controlled aseptic conditions. Adequate anaesthesia should be given to the patient prior to the procedure. The pupil of the eye to be injected must be dilated and a broad-spectrum microbicide should be topically administered prior to the surgery according to standard medical practice.

For instructions for preparation, accidental exposure to and disposal of Luxturna, see section 6.6.

Administration

Follow the steps below to administer voretigene neparvovec to patients:

• Diluted Luxturna should be inspected visually prior to administration. If particulates, cloudiness, or discoloration are visible, the medicinal product must not be used.
• Connect the syringe containing the diluted product to the extension tube and subretinal injection cannula. The product is slowly injected through the extension tube and subretinal injection cannula to eliminate any air bubbles in the system.
• The volume of product available for injection is confirmed in the syringe, by aligning the plunger tip with the line that marks 0.3 mL.
• After vitrectomy is completed, Luxturna is administered by subretinal injection using a subretinal injection cannula introduced via pars plana (Figure 1A).
• Under direct visualisation, the tip of the subretinal injection cannula is placed in contact with the retinal surface. The recommended site of injection should be located along the superior vascular arcade, at least 2 mm distal to the centre of the fovea (Figure 1B). A small amount of the product is slowly injected until an initial subretinal bleb is observed, and then the remaining volume is slowly injected until the total 0.3 mL is delivered.

Figure 1A. Subretinal injection cannula introduced via pars plana:

Figure 1B. Tip of the subretinal injection cannula placed within the recommended site of injection (surgeon's view):

• At the completion of the injection, the subretinal injection cannula is removed from the eye.
• After injection, any unused product must be discarded. The back-up syringe may not be retained.
• Fluid-air exchange is performed, carefully avoiding fluid drainage near the retinotomy created for the subretinal injection.
• Supine head positioning is initiated immediately in the post-operative period and upon discharge should be maintained by the patient for 24 hours.

There is no clinical experience with overdose of voretigene neparvovec. Symptomatic and supportive treatment, as deemed necessary by the treating physician, is advised in case of overdose.

Unopened frozen vials:

3 years.

After thawing:

Once thawed, the medicinal product should not be re-frozen and should be left at room temperature (below 25°C).

After dilution:

Following dilution under aseptic conditions, the solution must be used immediately; if not used immediately, the storage time at room temperature (below 25°C) should be no longer than 4 hours.

Concentrate and solvent must be stored and transported frozen at ≤-65°C.

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

Concentrate:

0.5 mL extractable volume of concentrate in 2 mL cyclic olefin polymer vial with a chlorobutyl rubber stopper sealed in place with an aluminium flip-off seal.

Solvent:

1.7 mL extractable volume of solvent in a 2 mL cyclic olefin polymer vial with a chlorobutyl rubber stopper sealed in place with an aluminium flip-off seal.

Each foil pouch includes a carton containing 1 vial of concentrate of 0.5 mL and 2 vials of solvent (each containing 1.7 mL).

Precaution to be taken before handling or administering the medicinal product

This medicinal product contains genetically modified organisms. Personal protective equipment (to include laboratory coat, safety glasses and gloves) should be worn while handling or administering voretigene neparvovec.

Preparation prior to administration

Each pack contains 1 vial of concentrate and 2 vials of solvent for single use only.

Luxturna should be inspected visually prior to administration. If particulates, cloudiness, or discoloration are visible, the single-dose vial must not be used.

Preparation of Luxturna should be performed within 4 hours of beginning the administration procedure, in accordance with the following recommended procedure performed under aseptic conditions.

Thaw one single-dose vial of concentrate and two vials of solvent at room temperature. Once all 3 vials (1 vial of concentrate and 2 vials of diluent) are thawed, dilution should be initiated. Gently invert the vials five times to mix the contents.

Inspect for any visual particulates or any anomalies. Any anomalies or appearance of visual particulates should be reported to the Marketing Authorisation Holder and product should not be used.

Transfer 2.7 mL of solvent taken from the two thawed vials and dispense into a sterile 10 mL empty glass vial using a 3 mL syringe.

For dilution, draw 0.3 mL of thawed concentrate into a 1 mL syringe and add it to the 10 mL sterile vial containing the solvent. Gently invert the vial at least five times for proper mixing. Inspect for any visual particulates. The diluted solution should be clear to slightly opalescent. Label the 10 mL glass vial containing the diluted concentrate as follows: 'Diluted Luxturna'.

Do not prepare syringes if the vial shows any damage or if any visual particulates are observed. Prepare the syringes for injection by drawing 0.8 mL of the diluted solution into a sterile 1 mL syringe. Repeat the same procedure to prepare a backup syringe. The product-filled syringes should then be transferred in a designated transport container to the surgical suite.

Measures to take in case of accidental exposure

Accidental exposure must be avoided. Local biosafety guidelines for preparation, administration and handling of voretigene neparvovec should be followed.

• Personal protective equipment (to include laboratory coat, safety glasses and gloves) should be worn while handling or administering voretigene neparvovec.
• Accidental exposure to voretigene neparvovec, including contact with skin, eyes and mucous membranes, is to be avoided. Any exposed wounds should be covered before handling.
• All spills of voretigene neparvovec must be treated with a virucidal agent such as 1% sodium hypochlorite and blot using absorbent materials.
• All materials that may have come in contact with voretigene neparvovec (e.g. vial, syringe, needle, cotton gauze, gloves, masks or dressings) must be disposed of in accordance with local biosafety guidelines.

Accidental exposure

• In the event of an accidental occupational exposure (e.g. through a splash to the eyes or mucous membranes), flush with clean water for at least 5 minutes.
• In the event of exposure to broken skin or needlestick injury, clean the affected area thoroughly with soap and water and/or a disinfectant.

Precautions to be taken for the disposal of the medicinal product

This medicinal product contains genetically modified organisms. Unused medicinal product or waste material must be disposed of in compliance with the local guidance for pharmaceutical waste.