Voretigene neparvovec, sold under the brand name Luxturna, is a medication used for the treatment of certain inherited retinal diseases caused by mutations in the RPE65 gene. These conditions, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP), can lead to progressive vision loss and eventually blindness.

With the use of a virus-based gene therapy called Voretigene Neparvovec, retinal cells can produce more physiologically active RPE65 by receiving a normal copy of the gene encoding the human retinal pigment epithelium 65 kDa protein (RPE65).

It is used to treat confirmed retinal dystrophy caused by a biallelic RPE65 mutation (Leber's congenital amaurosis).

Voretigene neparvovec Dose in Adults

Voretigene neparvovec Dosage in the therapy of Retinal dystrophy:  

Subretinal:

• The dose involves injecting 1.5 x 10 vector genomes in a small amount (0.3 mL) into each eye.
• These injections are done on separate days, with at least 6 days between each injection.

Voretigene neparvovec Dosage of concomitant medications:  

• Along with Voretigene neparvovec, patients may also take other medications.
• Specifically, they may be prescribed oral corticosteroids, like prednisone, to reduce the risk of inflammation or immune reactions.
• The recommended dose is 1 mg per kilogram of body weight per day, up to a maximum of 40 mg per day.
• Patients typically take these steroids for 7 days, starting 3 days before the first eye injection.
• Then, the dosage is gradually reduced over the next 10 days.
• The same corticosteroid regimen applies to the second eye injection.
• If the steroid taper for the first eye is not complete 3 days before the planned second eye injection, the same steroid regimen is followed for the second eye, replacing the taper for the first eye.

Voretigene neparvovec Dose in Children

• Before the first injection into the first eye, start taking oral corticosteroids like prednisone, beginning 3 days earlier.
• The dose is 1 mg per kilogram of body weight per day, up to a maximum of 40 mg per day, for 7 days.
• Then, gradually decrease the dose over the next 10 days.
• The same corticosteroid schedule applies to the second eye injection.
• If the steroid taper for the first eye isn't finished 3 days before the planned second eye injection, use the same steroid regimen for the second eye instead of tapering for the first eye.

Voretigene neparvovec Dosage in the treatment of Retinal dystrophy:  

For children and adolescents being treated for retinal dystrophy:

• The dose of Voretigene neparvovec involves injecting 1.5 x 10 vector genomes in a small amount (0.3 mL) into each eye.
• These injections are given on separate days, with at least 6 days between each injection.
• In clinical trials, the youngest patients were 4 years old.

Pregnancy Risk Factor: C

• Studies regarding the reproductive effects of Voretigene neparvovec on animals have not been carried out.

Voretigene neparvovec use during breastfeeding:

• It's uncertain whether Voretigene neparvovec is present in breast milk.
• According to the manufacturer, if you're breastfeeding and considering this therapy, you should weigh the potential risk of your infant being exposed to the medication against the benefits of breastfeeding for your baby and the benefits of treatment for you.

Voretigene neparvovec Dose in Renal Disease:

• The manufacturer's labeling doesn't provide dosage adjustments for renal impairment since it hasn't been studied.
• However, no adjustment is expected because there's minimal systemic absorption of the medication.

Voretigene neparvovec Dose in Liver Disease:

• The manufacturer's labeling doesn't include dosage adjustments for hepatic impairment since it hasn't been studied.
• However, it's anticipated that no adjustment is needed because there's minimal systemic absorption of the medication.

Common Side Effects of Voretigene neparvovec Include:

• Ophthalmic:
  • Increased Intraocular Pressure
  • Conjunctival Hyperemia
  • Cataract

Less Common Side Effects of Voretigene neparvovec Include:

• Ophthalmic:
  • Eye Disease
  • Retinal Deposits
  • Retinal Hemorrhage
  • Retinopathy
  • Retinal Pigment Epithelium Tear
  • Corneal Thinning
  • Eye Irritation
  • Eye Pain
  • Endophthalmitis
  • Maculopathy
  • Ophthalmic Inflammation
  • Retinal Changes

Contraindication to Voretigene neparvovec Include:

• The manufacturer's labeling does not list any contraindications for the use of Voretigene neparvovec.

Warnings and precautions

Cataracts

• Subretinal injection, especially in conjunction with vitrectomy surgery, may raise the risk of developing or worsening cataracts.

Endophthalmitis

• Endophthalmitis, an inflammation of the inner layers of the eye, can happen after intraocular surgical procedures or injections.
• It's crucial to use proper sterile injection techniques to minimize this risk.
• Patients should be monitored for any signs or symptoms of infection or inflammation following the procedure.

Increased intraocular pressure

• After a subretinal injection, there might be an increase in intraocular pressure (IOP).
• It's important to monitor the patient's intraocular pressure following the injection.

Anomalies of the retina:

• During or after a subretinal injection or vitrectomy, there's a risk of retinal abnormalities, including macular holes, foveal thinning, loss of foveal function, foveal dehiscence, retinal hemorrhage, retinal tears, epiretinal membrane, and retinal detachment.
• Patients should be monitored for macular abnormalities, retinal tears, or detachment.
• It's important to avoid administering the injection in the immediate vicinity of the fovea, the central part of the retina responsible for sharp central vision.

Vision loss:

• Expansion of the intraocular air bubble, which is sometimes used in procedures like vitrectomy, may result in irreversible vision loss.
• It's crucial to avoid activities that could cause changes in pressure, such as air travel, traveling to high elevations, or scuba diving, until the air bubble has completely dissipated.
• This process might take a week or longer following the injection.
• Ophthalmic examination should confirm the dissipation of the air bubble.
• Additionally, patients should be monitored for any visual disturbances, as permanent decline in visual acuity may occur.

Monitor:

Increase in Intraocular Pressure:

• Following the injection, there might be a rise in eye pressure.
• Monitor the patient's eye pressure after the injection.

Retinal Abnormalities:

• Injection procedures may lead to various retinal issues such as macular holes, thinning of the fovea, loss of foveal function, retinal hemorrhage, tears, or detachment.
• Watch for any signs of these abnormalities and seek medical attention if they occur.

Signs/Symptoms of Infection or Inflammation:

• Be vigilant for any signs or symptoms of infection or inflammation, especially after the injection.
• If any signs like redness, pain, or swelling occur, contact a healthcare provider promptly.

Visual Disturbance:

• Patients may experience visual disturbances, such as blurred vision or difficulty seeing.

How to administer Voretigene neparvovec?

Preparation for Subretinal Injection:

• Apply a topical broad-spectrum microbiocide to the conjunctiva, cornea, and eyelids before the surgery.

Injection Technique:

• Inject along the superior vascular arcade, at least 2 mm distal to the center of the fovea.
• Avoid direct contact with the retinal vasculature or areas of pathologic features, such as dense atrophy or intraretinal migration.
• Inject a small amount of product slowly until an initial subretinal bleb is observed.
• Slowly inject the remaining volume until the total 0.3 mL is delivered.

Post-Injection Care:

• Immediately after the injection, position the head supinely.
• Rest in a supine position as much as possible for the next 24 hours.

Mechanism of action of Voretigene neparvovec:

• Voretigene neparvovec is a gene therapy that uses an adeno-associated virus vector to deliver a healthy version of the gene responsible for producing a protein called retinal pigment epithelial 65 kDa (RPE65) to retinal cells.
• This therapy aims to supplement or replace the deficient or missing RPE65 protein in individuals with certain genetic mutations.
• These mutations result in decreased or absent levels of RPE65, which is crucial for the visual cycle in the retina.
• Without sufficient RPE65 activity, the visual cycle is disrupted, leading to impaired vision.
• By introducing the correct gene, voretigene neparvovec restores RPE65 function and helps improve vision in affected individuals.

Absorption:

• Voretigene neparvovec has minimal absorption.

International Brands of Voretigene neparvovec:

• Luxturna

Voretigene neparvovec Brands in Pakistan:

Not available in Pakistan