LUXTURNA

Treatment should be initiated and administered by a retinal surgeon experienced in performing macular surgery. 5 × 1011 vector genomes voretigene neparvovec in each eye. 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.

5 mg/kg every other day (maximum of 20 mg/day) 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. 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. 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. 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. 6. Administration Follow the steps below to administer voretigene neparvovec to patients: • Diluted Luxturna should be inspected visually prior to administration.

Summary of the safety profile In the phase 1 and phase 3 clinical studies, there were three non-serious adverse reactions of retinal deposits in three of 41 (7%) subjects that were considered to be related to voretigene neparvovec.

All three of these events were a transient appearance of asymptomatic subretinal precipitates inferior to the retinal injection site, 1-6 days after injection and resolved without sequelae. Serious adverse reactions related to the administration procedure were reported in three subjects.

One of 41 (2%) subjects reported a serious event of intraocular pressure increased (secondary to administration of depo-steroid) that was associated with treatment for endophthalmitis related to the administration procedure and resulted in optic atrophy, and one of 41 (2%) subjects reported a serious event of retinal disorder (loss of foveal function) that was assessed as related to the administration procedure.

One of 41 (2%) subjects reported a serious event of retinal detachment that was assessed as related to the administration procedure. The most common adverse reactions (incidence ≥5%) related to the administration procedure were conjunctival hyperaemia, cataract, increased intraocular pressure, retinal tear, dellen, macular hole, subretinal deposits, eye inflammation, eye irritation, eye pain and maculopathy (wrinkling on the surface of the macula).

Tabulated list of adverse reactions The adverse reactions are listed by system organ class and frequency using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data).

Table 2 Adverse reactions related to voretigene neparvovec System organ class Frequency Adverse reaction Common Retinal depositsEye disorders Not known Chorioretinal atrophy* *Includes retinal degeneration, retinal depigmentation and injection site atrophy Table 3 Adverse reactions related to administration procedure System organ class Frequency Adverse reactions Psychiatric disorders Common Anxiety Nervous system disorders Common Headache, dizziness Very common Conjunctival hyperaemia, cataract Common Retinal tear, dellen, macular hole, eye inflammation, eye irritation, eye pain, maculopathy, choroidal haemorrhage, conjunctival cyst, eye disorder, eye swelling, foreign body sensation in eyes, macular degeneration, endophthalmitis, retinal detachment, retinal disorder, retinal haemorrhage Eye disorders Not known Vitreous opacities, chorioretinal atrophy* Gastrointestinal disorders Common Nausea, vomiting, abdominal pain upper, lip pain Skin and subcutaneous tissue disorders Common Rash, swelling face Very common Intraocular pressure increased Investigations Common Electrocardiogram T wave inversion Injury, poisoning and procedural complications Common Endotracheal intubation complication, wound dehiscence *Includes retinal degeneration, retinal depigmentation and injection site atrophy Description of select adverse reactions Chorioretinal atrophy Chorioretinal atrophy has been reported as an adverse reaction during post-marketing experience and reported as progressive in some patients.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Subretinal injection-related reactions Proper aseptic techniques should always be used for the preparation and administration of Luxturna.

The following adverse reactions have been observed with the administration procedure: • Eye inflammation (including endophthalmitis), retinal tear and retinal detachment. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.

• Retinal disorder (foveal thinning, loss of foveal function), macular hole, maculopathy (epiretinal membrane, macular pucker) and eye disorder (foveal dehiscence). • Increase in intraocular pressure. Intraocular pressure should be monitored prior to and following administration of the medicinal product and managed appropriately.

Patients should be instructed to avoid air travel or other travel to high elevations until the air bubble formed as a result of administration of Luxturna has completely dissipated from the eye. A time period of up to one week or more following injection may be required before dissipation of the air bubble; this should be verified on ophthalmic examination.

A rapid increase in altitude while the air bubble is still present can cause a rise in eye pressure and irreversible vision loss. 8), may occur during the weeks that follow the treatment. Patients should be instructed to contact their healthcare professional if visual disturbances persist.

Patients should avoid swimming because of an increased risk of infection in the eye. Patients should avoid strenuous physical activity because of an increased risk of injury to the eye. Patients may resume swimming and strenuous activity, after a minimum of one to two weeks, on the advice of their healthcare professional.

1. Ocular or periocular infection. Active intraocular inflammation.