Luxturna 5 x 10¹² genomas vectoriales/ml concentrado y disolvente para solucion inyectable

Label: information for the patient

Luxturna 5×1012vectorial genomes/ml concentrated and solvent for injectable solution

voretigén neparvovec

This medication is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you experience. The final part of section4 includes information on how to report these adverse effects.

Read this label carefully before this medication is administered to you, because it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this label. See section4.

Luxturna is a gene therapy product that contains the active substance voretigene neparvovec.

Luxturna is used for the treatment of adults and children with vision loss due to inherited retinal dystrophy caused by mutations in the RPE65 gene.RPE65.These mutations prevent the body from producing a protein necessary for vision and lead to vision loss and possible blindness.

The active ingredient of Luxturna, voretigene neparvovec, is a modified virus that contains a copy of the RPE65 gene.RPE65. After injection, this gene reaches the retina cells, the layer at the back of the eye that detects light. This allows the retina to produce the proteins necessary for vision. The virus used to administer the gene does not cause disease in humans.

Luxturna will only be administered if genetic tests show that your vision loss is caused by mutations in the RPE65 gene.

You should not receive Luxturna

• If you are allergic to voretigene neparvovec or any of the other components of this medication (listed in section6)
• If you have an eye infection
• If you have eye inflammation

If you are affected by any of the above situations, or if you are unsure, consult your doctor before Luxturna is administered to you.

Warnings and precautions

Before receiving treatment with Luxturna:

• Inform your doctor if you have signs of eye infection or eye inflammation, for example if you have eye redness, light sensitivity, eye swelling, or eye pain.
• Inform your doctor if you have an active infection of any type. Your doctor may delay your treatment until the infection clears up because this medication may make it harder to fight the infection. See also section3.

After receiving treatment with Luxturna:

• Consult your doctor immediately if your eye/eyes turn red, if you feel eye pain, light sensitivity, see flashes or floaters, or if you notice a worsening or blurry vision.
• You should avoid air travel or other high-altitude travel until your doctor tells you to do so. During treatment with this medication, your doctor inserts an air bubble into your eye, which your body absorbs slowly. Until the bubble is completely absorbed, air travel or other high-altitude travel may cause the bubble to grow and cause eye damage, including vision loss. Consult your doctor before traveling.

• You should avoid swimming due to a higher risk of eye infection. Consult your doctor before swimming after receiving treatment with Luxturna.
• You should avoid strenuous physical activity due to a higher risk of eye injury. Consult your doctor before starting strenuous physical activity after receiving treatment with Luxturna.
• You may experience transient visual changes, such as light sensitivity and blurry vision. Inform your doctor about any visual changes you experience. Your doctor can help you reduce any discomfort caused by these transient changes.
• The active ingredient in Luxturna may be temporarily excreted in tears. You and your caregiver must place the dressings and disposal materials that have come into contact with tears and nasal secretions in sealed bags before disposing of them. You should follow these precautions for 14days.
• You will not be able to donate blood, organs, tissues, and cells for transplantation after being treated with Luxturna.

Children and adolescents

Luxturna has not been studied in children under four years of age. Data is limited.

Other medications and Luxturna

Inform your doctor if you are taking, have recently taken, or may need to take any other medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or nurse before receiving treatment with Luxturna.

The effects of this medication on pregnancy and the fetus are unknown. As a precaution, you should not receive Luxturna while pregnant.

Luxturna has not been studied in lactating women. It is not known if it passes into breast milk. Inform your doctor if you are breastfeeding or plan to do so. Your doctor will help you decide whether to stop breastfeeding or not receive Luxturna, taking into account the benefits of breastfeeding for your baby and the benefits of Luxturna for you.

Driving and operating machinery

You may experience transient visual changes after receiving Luxturna. Do not drive or operate heavy machinery until your vision has recovered. Consult your doctor before resuming these activities.

Luxturna contains sodium

This medication contains less than 1mmol of sodium (23mg) per dose, which is essentially "sodium-free".

Luxturna will be administered to you in an operating room by experienced eye surgeons. Luxturna is administered under anesthesia. Your doctor will discuss anesthesia and how it will be administered with you.

Your doctor will perform eye surgery to remove the clear gel that occupies the interior of your eye, and then inject Luxturna directly into the retina, the thin light-sensitive layer located at the back of your eye. This procedure will be repeated in the other eye at least 6 days later. You will need to stay in postoperative observation for several hours after each procedure to monitor your recovery and observe any side effects of the surgery or anesthesia.

Before starting treatment with Luxturna, your doctor may ask you to take a medication that suppresses your immune system (your body's natural defenses) so that it does not try to fight Luxturna when it is administered. It is essential that you take this medication according to the instructions provided by your doctor. Do not stop taking the medication without consulting your doctor first.

If you receive more Luxturna than you should

Since this medication will be administered by a doctor, it is unlikely that you will receive more medication than you should. If this occurs, your doctor will treat any symptoms as necessary. Inform your doctor or nurse if you experience any vision problems.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following side effects related to Luxturna may occur:

Frequent (may affect up to 1 in 10 people)

• Deposits under the retina

Unknown frequency (cannot be estimated from available data)

• Atrophy of the (corio)retina

The following side effects related to the injection procedure may occur:

Very frequent (may affect more than 1 in 10 people)

• Redness of the eyes
• Cataract (opacity of the crystalline lens)
• Increased eye pressure

Frequent (may affect up to 1 in 10 people)

• Retinal tear
• Eye pain
• Swelling of the eyes
• Retinal detachment
• Bleeding in the back of the eye
• Eye pain or increased discomfort
• Blurred vision due to a hole in the retina
• Thin surface of the eye (dellen)
• Ocular irritation
• Ocular inflammation
• Sensation of a foreign body in the eye
• Ocular discomfort
• Abnormalities in the back of the eye
• Nausea (desire to vomit), vomiting, abdominal (stomach) pain, lip pain
• Change in heart electrical activity
• Headache, dizziness
• Skin rash, facial swelling
• Anxiety
• Problems associated with the placement of a breathing tube in the trachea
• Surgical wound rupture

Unknown (frequency cannot be estimated from available data)

• Clouding of the gelatinous substance found inside the eye (vitreous opacities)
• Atrophy of the (corio)retina

The damage to the eye tissues may be accompanied by bleeding, inflammation, and a higher risk of infection. A reduction in vision occurs in the days following surgery, which generally improves; inform your doctor if vision does not return.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Luxturna will be conserved by healthcare professionals in their healthcare center.

The concentrate and solvent must be transported and stored frozen at a temperature≤‑65°C. Once thawed, the medication must not be re-frozen and must be stored at room temperature (below 25°C).

Do not use this medication after the expiration date that appears on the label and in the box after CAD.

Composition of Luxturna

• The active ingredient is voretigene neparvovec. Each milliliter of concentrate contains 5 × 10^12 vector genomes (vg). The concentrate (single-dose vial of 2 mL with extractable volume of 0.5 mL) requires a 1:10 dilution before administration.
• Each dose of diluted solution contains 1.5 × 10^11 vector genomes of voretigene neparvovec in a usable volume of 0.3 mL.
• The other excipients of the concentrate are sodium chloride (see "Luxturna contains sodium" at the end of section 2 of this leaflet), sodium dihydrogen phosphate monohydrate (to adjust pH), sodium dihydrogen phosphate dihydrate (to adjust pH), poloxamer 188, and water for injection.
• The solvent contains sodium chloride (see the end of section 2), sodium dihydrogen phosphate monohydrate (to adjust pH), sodium dihydrogen phosphate dihydrate (to adjust pH), poloxamer 188, and water for injection.

This medicine contains genetically modified organisms.

Appearance of Luxturna and contents of the pack

Luxturna is a clear and colorless concentrate for subretinal injection solution that is presented in a transparent plastic vial. The solvent is a transparent and colorless liquid that is presented in a transparent plastic vial.

Each aluminum pouch contains a cardboard box that includes 1 vial of 0.5 mL of concentrate and 2 vials of solvent (each containing 1.7 mL).

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible Person

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Last update of this leaflet:

Other sources of information

This leaflet is available in audio file format and in large print on the website:http://www.voretigeneneparvovec.support

Further detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

Precautions to be taken before handling or administering the medicine

This medicine contains genetically modified organisms. Use personal protective equipment (including a laboratory coat, safety glasses, and gloves) while preparing or administering voretigene neparvovec.

Appropriate intraocular pressure control should be ensured and monitored before and after administration of the medicine.

After administration, patients should be instructed to notify immediately any symptoms suggesting endophthalmitis or retinal detachment and should be treated accordingly.

Preparation before administration

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

Luxturna should be visually inspected before administration. If particles, turbidity, or discoloration are detected, the single-dose vial should not be used.

The preparation of Luxturna should be carried out within 4 hours prior to the start of the administration procedure, in aseptic conditions, and in accordance with the following recommended procedure.

Allow the contents of a single-dose vial of concentrate and two vials of solvent to thaw at room temperature.Once thawed, the three vials (1 vial of concentrate and 2 vials of solvent) should be diluted.Invert the vials gently five times to mix the contents.

Inspect for visible particles or any anomalies. The appearance of any anomalies or visible particles should be reported to the Marketing Authorization Holder and the product should not be used.

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

To dilute, extract 0.3 mL of thawed concentrate with a 1 mL syringe and add to the sterile 10 mL vial containing the solvent. Invert the vial gently at least five times to ensure adequate mixing. Inspect for visible particles. The diluted solution should be clear or slightly opalescent. Label the 10 mL glass vial containing the diluted concentrate as follows: "Luxturna diluted".

Do not prepare syringes if the vial shows any damage or if visible particles are observed. Prepare syringes for injection by extracting 0.8 mL of the diluted solution into a sterile 1 mL syringe. Repeat the same procedure to prepare a spare syringe. The filled syringes should be transported to the operating room in a designated container.

Measures to be taken in case of accidental exposure

Accidental exposure should be avoided. Follow local regulations on biosecurity for the preparation, administration, and handling of voretigene neparvovec.

• Use personal protective equipment (including a laboratory coat, safety glasses, and gloves) while handling or administering voretigene neparvovec.
• Avoid accidental exposure to voretigene neparvovec, including contact with the skin, eyes, and mucous membranes. Cover any wounds before handling this medicine.
• Any spill of voretigene neparvovec should be treated with a virucidal agent, such as sodium hypochlorite 1%, and dried with absorbent materials.
• All materials that may have come into contact with voretigene neparvovec (e.g., vial, syringe, needle, cotton balls, gloves, masks, or bandages) should be disposed of in accordance with local biosecurity regulations.

Accidental exposure

• In case of occupational accidental exposure (e.g., splashing in the eyes or mucous membranes), the affected area should be flushed with clean water for at least 5 minutes.
• In case of exposure to a wounded skin or puncture wound with the needle, the affected area should be cleaned thoroughly with water and soap and/or a disinfectant.

Precautions to be taken in the disposal of the medicine

This medicine contains genetically modified organisms. The disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations on pharmaceutical waste.

Dosage

The treatment should be initiated and administered by an experienced retinal surgeon.

Patients will receive a single dose of voretigene neparvovec of 1.5 × 10^11 vector genomes in each eye. Each dose should be administered within the subretinal space in a total volume of 0.3 mL. Administration should be carried out individually in each eye on separate days, with at least a 6-day interval between each surgical procedure.

Immunomodulatory regimen

Before initiating the immunomodulatory regimen and before administration of voretigene neparvovec, the patient should be examined to detect symptoms of active infection of any nature, and in the event of such an infection, the start of treatment should be postponed until the patient has recovered.

An immunomodulatory regimen is recommended to be initiated 3 days before administration of voretigene neparvovec in the first eye, following the schedule described below (Table 1). The start of the immunomodulatory regimen for the second eye should follow the same schedule and should replace the immunomodulatory regimen of the first eye.

Table 1Immunomodulatory regimen pre and postoperative for each eye

Special populations

Geriatric patients

No safety and efficacy of voretigene neparvovec have been established in patients ≥ 65 years. Data are limited. However, no dose adjustment is required in elderly patients.

Patients with hepatic and renal impairment

No safety and efficacy of voretigene neparvovec have been established in patients with hepatic or renal impairment. No dose adjustment is required in these patients (see section 5.2).

Pediatric population

No safety and efficacy of voretigene neparvovec have been established in children under 4 years of age. Data are limited. No dose adjustment is required in pediatric patients.

Administration

Subretinal use.

Luxturna is a sterile concentrated solution for subretinal injection that requires thawing and dilution before administration.

This medicine should not be administered by intravitreal injection.

Luxturna is a single-use vial for a single administration in one eye. The product is administered by subretinal injection after vitrectomy in each eye. It should not be administered too close to the fovea to maintain foveal integrity.

Voretigene neparvovec should be administered in the operating room under controlled aseptic conditions. Before the procedure, the patient should be administered appropriate anesthesia. The pupil of the eye to be administered the injection should be dilated, and before surgery, a broad-spectrum antibiotic should be administered topically according to standard medical practice.

Administration

Follow the steps below to administer voretigene neparvovec to patients:

• Once diluted, Luxturna should be visually inspected before administration. If particles, turbidity, or discoloration are observed, the medicine should not be used.
• Connect the syringe containing the diluted product to the extension tube and the subretinal injection cannula. The product should be injected slowly through the extension tube and the subretinal injection cannula to eliminate any air bubbles in the system.
• The volume of product available for injection should be confirmed in the syringe by aligning the tip of the plunger with the line marking 0.3 mL.
• Once vitrectomy is complete, Luxturna is administered by subretinal injection using a subretinal injection cannula introduced via the pars plana.
• Under direct visualization, the tip of the subretinal injection cannula should be placed in contact with the retinal surface. The recommended injection site should be located along the superior vascular arcade, at least 2 mm from the center of the fovea. A small amount of product should be injected slowly until an initial subretinal bubble is observed, and then the remaining volume should be injected slowly until the total 0.3 mL is administered (Figure 1).

Figure 1Tip of the subretinal injection cannula placed at the recommended injection site (surgical view)

• After injection, the subretinal injection cannula should be removed from the eye.
• After injection, any unused product should be discarded. The spare syringe should not be stored.
• Careful fluid-air exchange should be performed, avoiding drainage of fluid near the retinotomy created for the subretinal injection.
• In the postoperative period, the patient's head should be positioned supine immediately and maintained for 24 hours after discharge.