Luxturna^® (Concentrate) Instructions for Use

Marketing Authorization Holder

Novartis Pharma AG (Switzerland)

Manufactured By

NOVA LABORATOIRES, Ltd. (United Kingdom)

Labeled By

CATALENT U.K. PACKAGING, Limited (United Kingdom)

Quality Control Release

NOVARTIS PHARMA, GmbH (Germany)

ATC Code

S01XA27 (Vortetigen nepavovek)

Active Substance

Voretigene neparvovec (Rec.INN registered by WHO)

Dosage Form

Luxturna®

Concentrate and diluent for solution for subretinal administration 5×1012 vector genomes/ml: fl. 0.5 ml 1 pc. (concentrate) and fl. 1.7 ml 2 pcs. (diluent)

Dosage Form, Packaging, and Composition

Concentrate for solution for subretinal administration – frozen solution; after thawing – a clear, colorless solution, free from foreign particles.

1 dose contains 1.5×10¹¹ vector genomes of voretigene neparvovec in a total volume of 0.3 ml.

Excipients : sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dihydrate, poloxamer 188, water for injections.

Diluent for solution for subretinal administration – frozen solution; after thawing – a clear, colorless solution, free from foreign particles.

Excipients : sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dihydrate, poloxamer 188, water for injections.

0.5 ml – polymer bottles (1) in a kit with diluent (fl. 1.7 ml 2 pcs.) – cardboard packs.

Clinical-Pharmacological Group

Drug improving microcirculation. Angioprotector

Pharmacotherapeutic Group

Other preparations for the treatment of eye diseases

Pharmacological Action

It is a gene therapy agent. It is used to treat adults and children with vision loss due to hereditary retinal dystrophy caused by mutations in the RPE65 gene. These mutations prevent the body from producing the protein necessary for vision, leading to vision loss and possible blindness.

Voretigene neparvovec is a modified virus containing a working copy of the RPE65 gene, which, after injection, delivers this gene into retinal cells (the tissue on the inside of the back of the eye that perceives light signals). This gives the retina the ability to produce the proteins necessary for vision. The virus used to deliver the genes does not cause human diseases.

This agent is used only if the results of genetic testing show that vision loss is due to mutations in the RPE65 gene.

Indications

For the treatment of adults and children with vision loss due to hereditary retinal dystrophy caused by mutations in the RPE65 gene.

ICD codes

Dosage Regimen

For subretinal administration only.

Administer as a single dose to each affected eye.

The dose for one eye is 1.5×10¹¹ vector genomes in a total volume of 0.3 ml.

Prepare the dose by diluting the concentrate with the provided diluent.

Calculate the required volume of diluted product to achieve the correct dose.

Administer the dose within four hours after dilution.

Discard any unused portion of the medicinal product.

Perform the procedure under adequate anesthesia.

Utilize standard aseptic technique for intraocular injection.

Perform a vitrectomy prior to subretinal administration.

Administer the injection via a subretinal cannula.

Initiate a course of topical corticosteroids prior to surgery.

Continue topical corticosteroids post-operatively, tapering the dose as directed.

Administer to one eye at a time.

Schedule the administration for the second eye no sooner than six days after the first eye.

Prescribe and administer only by a retinal surgeon experienced in vitreoretinal surgery.

Adverse Reactions

Eye disorders very common – eye redness, lens opacity, increased intraocular pressure; common – subretinal deposits, retinal tear, thinning of the eye surface, disorders of the posterior eye segment, eye inflammation, eye irritation, visual impairment, conjunctival cyst, foreign body sensation in the eye, eye pain, eye swelling, retinal detachment; unknown – vitreous opacities, chorioretinal atrophy.

Gastrointestinal system disorders : common – nausea, vomiting, abdominal pain, lip pain.

Cardiovascular system disorders : common – changes in the electrical activity of the heart.

Nervous system disorders common – headache, dizziness, anxiety.

Skin and subcutaneous tissue disorders common – skin rash, facial swelling.

Procedure-related reactions common – problems related to the placement of a breathing tube in the trachea, surgical wound dehiscence.

Other damage to eye tissue may be accompanied by bleeding and swelling, as well as an increased risk of infection. In the postoperative days, a decrease in vision is observed, which usually recovers.

Contraindications

Hypersensitivity to the active substance; eye infection; inflammatory eye disease.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

The safety and efficacy of voretigene neparvovec in patients with hepatic impairment have not been established. Dose adjustment in these patients is not required.

Use in Renal Impairment

The safety and efficacy of voretigene neparvovec in patients with renal impairment have not been established. Dose adjustment in these patients is not required.

Pediatric Use

Use in children under 4 years of age has not been studied. Data are not available. Dose adjustment in children is not required.

Geriatric Use

Dose adjustment in elderly patients over 65 years of age is not required.

Special Precautions

Before starting the course of immunomodulatory therapy and administration of this agent, the patient should be examined for symptoms of an active infectious disease of any etiology. If such an infection is present, treatment should be postponed until the patient recovers.

After administration of this agent, the patient should immediately consult a doctor if eye redness (both eyes), pain, sensitivity to light, sparks and floating “spots” in the field of vision, worsening and blurred vision develop.

The patient should refrain from air travel and any travel involving ascent to altitude until permitted by the treating physician. Consult a doctor before planning travel.

Swimming should be avoided due to the increased risk of eye infection. The patient should consult a doctor before swimming after administration of this agent.

Intense physical activity should be avoided due to the increased risk of eye injury. Consult a doctor before resuming intense physical activity after administration of this agent.

In some cases, cataracts may develop, which can lead to blurred vision. The development of cataracts or worsening of pre-existing cataracts is a known complication of eye surgery required before administration of this agent. There is an additional risk of cataract development if the lens is damaged by the needle for injection into the back of the eye.

Patients, caregivers, especially pregnant and breastfeeding women, and individuals with suppressed immune systems should wear gloves when changing dressings and disposing of dressings and other waste. These precautions should be observed for 14 days after treatment.

After treatment with this agent, the patient cannot become a donor of blood, organs, tissues, or cells for transplantation, since Voretigene neparvovec is a gene therapy agent.

The medicinal product contains genetically modified organisms.

Effect on ability to drive vehicles and operate machinery

After administration of this agent, temporary visual disturbances may occur. Do not drive vehicles or operate machinery until vision has recovered.

Storage Conditions

Store at or below -18 °C. Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.