Voretigene neparvovec for retinal dystrophy

Voretigene neparvovec is a virus vector-based gene therapy that gives a normal copy of the gene encoding human retinal pigment epithelial 65 kDa protein (RPE65) to retinal cells thus augmenting reduced or absent levels of biologically active RPE65.

It is used in the treatment of confirmed biallelic RPE65 mutation-associated retinal dystrophy (Leber's congenital amaurosis)

Voretigene neparvovec Dose in Adults

Dosage in the treatment of Retinal dystrophy:

Subretinal:

1.5 x 10 vector genomes are given in a total volume of 0.3 mL & injected into each eye on separate days within a close interval (But interval should be no fewer than 6 days apart)

Dosage of concomitant medications:

Systemic oral glucocorticoids equivalent to prednisone 1 mg/kg/day (maximum dose of 40 mg/day) are given for a total of seven days (starting 3 days before administration of voretigene neparvovec to the first eye) and is followed by tapering the dose during the following 10 days.
The same corticosteroid dosing regimen is applicable for giving to the second eye.
If the corticosteroid taper to the first eye is not complete within 3 days before planned administration to the second eye, the corticosteroid regimen for the second eye replaces the taper for the first eye.

Voretigene neparvovec Dose in Childrens

3 days before administration of the first dose in the first eye, start systemic oral corticosteroids equivalent to prednisone 1 mg/kg/day (maximum daily dose: 40 mg/day)
Steroids should be continued for a total of 7 days, then taper corticosteroid dose during the following 10 days.
The same corticosteroid dosing regimen is used for administration to the second eye.
If the corticosteroid taper to the first eye is not complete within 3 days before planned administration to the second eye, the corticosteroid regimen for the second eye replaces the taper for the first eye

Dosage in the treatment of Retinal dystrophy:

Children and Adolescents:
- Ophthalmic:
- A subretinal injection is given as 1.5 x 10 vector genomes in a 0.3 ml total volume injected into each eye on separate days within a close interval (no fewer than 6 days apart).

Pregnancy Risk Factor: C

Studies on animal reproduction have not been conducted.

Voretigene neparvovec use during breastfeeding:

It is unknown if voretigene Neparvovec is found in breast milk.
According to the manufacturer breastfeeding during therapy should be considered in order to minimize infant exposure and to maximize the benefits for the mother.

Voretigene neparvovec Dose in Renal Disease:

There are no dosage adjustments given in the manufacturer's labeling (has not been studied); however, no adjustment required due to minimal systemic absorption

Voretigene neparvovec Dose in Liver Disease:

There are no dosage adjustments given in the manufacturer's labeling (has not been studied); however, no adjustment required due to minimal systemic absorption.

Common Side Effects of Voretigene neparvovec Include:

Ophthalmic:
- Conjunctival Hyperemia
- Cataract
- Increased Intraocular Pressure

Less Common Side Effects of Voretigene neparvovec Include:

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

Contraindication to Voretigene neparvovec Include:

The manufacturer's labeling does not list any contraindications

Warnings and precautions

Cataracts
- Subretinal injections (especially vitrectomy) may increase the risk of cataract development or catract progression.
Endophthalmitis
- This may happen after intraocular surgery or injection.
- Use of aseptic injection techniques.
- Be on the lookout for signs and symptoms of inflammation or infection.
Increased intraocular pressure
- IOP can be increased following subretinal injection
- Monitor for IOP.
Anomalies of the retina:
- Vitrectomy or subretinal injection can cause retinal abnormalities, such as macular holes, foveal dysfunction, foveal hemorhage, foveal thinning, retinal tears and epiretinal membrane.
- Monitor for macular abnormalities, retinal tear or detachment.
- Avoid giving near fovea.
Vision loss:
- Irreversible vision loss can be caused by the expansion of an intraocular bubble.
- Avoid flying, travel to high altitudes and scuba dive until the air bubble has completely dissipated. This may take up to a week after injection.
- You can confirm the existence of air bubbles by performing an ophthalmic exam.
- A permanent decline in visual acuity may occur
- Monitoring for visual disturbances takes place

Monitor:

Increase in intraocular pressure is monitored
Retinal abnormalities may occur during or after the injection that may include macular holes, loss of foveal function, foveal thinning, foveal dehiscence, retinal hemorrhage, retinal tears, epiretinal membrane or retinal detachment
signs and symptoms of infection & visual disturbance are observed

How to administer Voretigene neparvovec?

It is administered via subretinal injection only.
Apply a topical broad-spectrum microbiocide to the conjunctiva, cornea, and eyelids before surgery.
Inject at least 2 mm distal to the center of the fovea, along the superior vascular arcade, avoiding direct contact with the retinal vasculature or areas of pathologic features.
Then Inject a small amount of product slowly until an initial subretinal bleb is observed
Remaining volume should be injected slowly until a total of 0.3 mL is delivered.
Following injection, start head positioning immediately.
Keep in a supine position as much as possible for the next 24 hours.

Mechanism of action of Voretigene neparvovec:

It is an adenoassociated virus vector-based gene treatment that delivers a normal copy the gene encoding human pigment epithelial 65kDa protein (RPE65), to retinal cells, thus increasing or reducing biologically active RPE65.
Mutations in the RPE65 gene can result in reduced or absent RPE65 isomerohydrolase activity
It can block the visual cycle, leading to vision impairment.

Absorption: Low