Luxturna (voretigene neparvovec) dosing, indications, interactions, adverse effects, and more

Sections

Sections voretigene neparvovec
Dosing & Uses
Adverse Effects
Warnings
Pregnancy
Pharmacology
Administration
Images
Patient Handout
Formulary

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

suspension for subretinal injection

0.5mL extractable volume per 2mL vial
Supplied concentration (ie, 5x10^12vg/mL) requires a 1:10 dilution before administration

Retinal Dystrophy

Indicated for confirmed biallelic RPE65 mutation-associated retinal dystrophy

Dose per eye: 1.5 x 10^11 vector genomes (vg) by subretinal injection in a total volume of 0.3 mL

Give subretinal administration to each eye on separate days within a close interval, but at least 6 days apart

Systemic oral corticosteroids

Start systemic oral corticosteroids equivalent to prednisone at 1 mg/kg/day (not to exceed 40 mg/day) for a total of 7 days
Initiate corticosteroid dosing regimen 3 days before administration to each eye; then taper dose during the next 10 days
Same corticosteroid dosing regimen applies for the administration of voretigene neparvovex-rzyl to the second eye
Taper corticosteroids
- If the corticosteroid taper following the first eye is not complete 3 days before the planned administration to the second eye, then the corticosteroid regimen for the second eye replaces the taper for the first eye

Dosage Forms & Strengths

suspension for subretinal injection

0.5mL extractable volume per 2mL vial
Supplied concentration (ie, 5x10^12vg/mL) requires a 1:10 dilution before administration

Retinal Dystrophy

Indicated for confirmed biallelic RPE65 mutation-associated retinal dystrophy

<1 year: Safety and efficacy not established

>1 year

Dose per eye: 1.5 x 10^11 vector genomes (vg) by subretinal injection in a total volume of 0.3 mL
Give subretinal administration to each eye on separate days within a close interval, but at least 6 days apart
See also Administration

Systemic oral corticosteroids

Start systemic oral corticosteroids equivalent to prednisone at 1 mg/kg/day (not to exceed 40 mg/day) for a total of 7 days
Initiate corticosteroid dosing regimen 3 days before administration to each eye; then taper dose during the next 10 days
Same corticosteroid dosing regimen applies for the administration of voretigene neparvovex-rzyl to the second eye
Taper corticosteroids
- If the corticosteroid taper following the first eye is not complete 3 days before the planned administration to the second eye, then the corticosteroid regimen for the second eye replaces the taper for the first eye

Safety and efficacy not established

Clinical studies did not include patients aged ≥65 years

>10%

Incidence based on by number of eyes treated

Cataract (19%)

Conjunctival hyperemia (11%)

1-10%

Incidence based on by number of eyes treated

Increased intraocular pressure (10%)

Retinal tear (5%)

Eye inflammation (5%)

Dellen (thinning of the corneal stroma) (4%)

Macular hole (4%)

Subretinal deposits (4%)

Maculopathy (wrinkling on the surface of the macula) (4%)

Eye irritation (2%)

Eye pain (2%)

Foveal thinning and loss of function (2%)

Endophthalmitis (1%)

Fovea dehiscence (separation of the retinal layers in the center of the macula) (1%)

Retinal hemorrhage (1%)

Postmarketing Reports

Eye disorders: Chorioretinal atrophy (also reported as retinal degeneration, retinal depigmentation, and injection site atrophy)

Contraindications

None

Cautions

Endophthalmitis may occur following any intraocular surgical procedure or injection; monitor and advise any signs or symptoms of infection or inflammation without delay

Permanent decline in visual acuity may occur following subretinal injection; monitor for visual disturbances

Retinal abnormalities (eg, macular holes, foveal thinning, loss of foveal function, foveal dehiscence, retinal hemorrhage) may occur; monitor and manage retinal abnormalities appropriately; do not administer voretigene neparvovex-rzyl in the immediate vicinity of the fovea

During or following vitrectomy, retinal abnormalities (eg, retinal tears, epiretinal membrane, retinal detachment) may occur; monitor during and following injection to permit early treatment of these retinal abnormalities; advise patients to report any signs or symptoms of retinal tears and/or detachment without delay

Increased intraocular pressure may occur

Avoid air travel, travel to high elevation or scuba diving until the air bubble formed following administration has completely dissipated from the eye; may take >1 week or more following injection for the air bubble to dissipate; changes in altitude while the air bubble is still present can result in irreversible vision loss

Subretinal injection of voretigene neparvovex-rzyl, especially vitrectomy surgery, is associated with an increased incidence of cataract development and/or progression

Pregnancy

Well-controlled human and animal reproductive studies with voretigene neparvovex-rzyl have not been conducted in pregnant women

No nonclinical or clinical studies were performed to evaluate the effect of voretigene neparvovex-rzyl on fertility

Lactation

No information regarding the presence of voretigene neparvovex-rzyl in human milk, the effects on the breastfed infant, or the effects on milk production

Development and health benefits of breastfeeding should be considered along with the mother’s clinical need for voretigene neparvovex-rzyl and any potential adverse effects on the breastfed infant from voretigene neparvovex-rzyl

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

RPE65 is produced in the retinal pigment epithelial (RPE) cells and converts all-trans-retinol to 11-cis-retinol, which subsequently forms the chomophore, 11-cis-retinal, during the visual (retinoid) cycle

Visual cycle is critical for biological conversion of a photon of light into an electrical signal in the retina

RPE65 gene mutations lead to reduced or absent levels of RPE65 isomerohydrolase activity, blocking the visual cycle and resulting in impairment of vision

An adeno-associated virus vector-based gene therapy designed to deliver a normal copy of the gene encoding the human retinal pigment epithelial 65-kd protein (RPE65) to cells of the retina in persons with reduced or absent levels of biologically active RPE65

Distribution

Biodistribution of voretigene neparvovex-rzyl was evaluated at 3 months following subretinal administration in nonhuman primates

Highest levels of vector DNA sequences were detected in intraocular fluids (anterior chamber fluid and vitreous) of vector-injected eyes

Low levels of vector DNA sequences were detected in the optic nerve of the vector-injected eye, optic chiasm, spleen, and liver, and, sporadically, in the lymph nodes

Vector DNA sequences were not detected in the gonads

Subretinal Preparation

Prepare voretigene neparvovex-rzyl within 4 hr of administration using sterile technique under aseptic conditions in a Class II vertical laminar flow biological safety cabinet (BSC)

Dilution

Thaw 1 single-dose vial of voretigene neparvovex-rzyl and 2 vials of diluent at room temperature
Mix thawed diluent vials by gently inverting them ~5 times
Visually inspect diluent and voretigene neparvovex-rzyl single-dose vials for particulates, cloudiness, or discoloration; do not use the vial(s) if particulates are present; new vial(s) of diluent should be used
Using the 3-mL syringe with 20G 1-inch needle, transfer 2.7 mL of diluent to 10-mL glass vial
Mix contents of thawed voretigene neparvovex-rzyl single-dose vial by gently inverting ~5 times
Draw 0.3 mL voretigene neparvovex-rzyl into a 1-mL sterile syringe with a 27G ½-inch sterile needle
Transfer 0.3 mL of voretigene neparvovex-rzyl to glass vial containing 2.7 mL of diluent
Gently invert the 10-mL glass vial approximately 5 time to mix contents
Label the 10-mL glass vial containing the diluted voretigene neparvovex-rzyl as follows: ‘Diluted LUXTURNA’

Preparation

To keep the syringes sterile, 2 operators are required for transfer of the contents of the 10-mL glass vial labeled ‘Diluted LUXTURNA’ into each of 2 sterile 1-mL syringes
Primary operator withdraws 0.8 mL of the diluted voretigene neparvovex-rzyl into a sterile 1-mL syringe using a 27G ½-inch sterile needle while the secondary operator holds the 10-mL glass vial
Prepare a total of two administration syringes
Label the first syringe “Diluted LUXTURNA” and label the second syringe “Backup Diluted LUXTURNA” using the sterile skin marker
The second syringe serves as a backup for the surgeon performing the subretinal administration procedure
Discard the backup syringe after surgery if not used
Visually inspect both syringes; if particulates, cloudiness, or discoloration are visible, do not use the syringe
Place the syringes into the sterile plastic bag after visual inspection and seal the bag
Place the sterile plastic bag with syringes containing diluted voretigene neparvovex-rzyl into an appropriate secondary container (eg, hard plastic cooler) for delivery to the surgical suite at room temperature

Subretinal Administration

For subretinal injection only

Items are required for administration

Syringe containing diluted voretigene neparvovex-rzyl
Subretinal injection cannula with a polyamide micro tip with an inner diameter of 41G
Extension tube made of polyvinyl chloride <6 inch (15.2 cm) in length and with an inner diameter <1.4 mm

Subretinal injection

Dilate eye and give adequate anesthesia to the patient
Administer a topical broad-spectrum microbiocide to the conjunctiva, cornea, and eyelids prior to surgery
Visually inspect voretigene neparvovex-rzyl prior to administration; if particulates, cloudiness, or discoloration are visible, do not use the product
Connect the syringe containing the diluted voretigene neparvovex-rzyl to the extension tube and subretinal injection cannula
Avoid excess priming volume; extension tube should not exceed 15.2 cm in length and 1.4 mm in inner diameter
Inject drug slowly through extension tube and subretinal injection cannula to eliminate any air bubbles
Confirm the volume of product available in the syringe for injection by aligning the plunger tip with the line that marks 0.3 mL
After completing a vitrectomy, identify the intended site of administration (see prescribing information for further illustrated information)
Recommended site of injection: Along the superior vascular arcade, >2 mm distal to the center of the fovea, avoiding direct contact with the retinal vasculature or with areas of pathologic features, such as dense atrophy or intraretinal pigment migration
Inject drug slowly until an initial subretinal bleb is observed; then inject remaining volume slowly until the total 0.3 mL is delivered
After completing the injection, remove subretinal injection cannula from the eye
Following injection, discard all unused product
Perform a fluid-air exchange, carefully avoiding fluid drainage near the retinotomy created for the subretinal injection
Initiate supine head positioning immediately in the postoperative period
Upon discharge, advise patients to rest in a supine position as much as possible for 24 hr

Storage

Drug and diluent: Store frozen at ≤-65°C

Following thaw of vials: Store at room temperature; further dilute and administer within 4 hr

Diluted drug: Store at room temperature just prior to injection procedure

Images

No images available for this drug.

Patient Handout

A Patient Handout is not currently available for this monograph.

Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

View explanations for tiers and restrictions

Tier	Description
1	This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2	This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC	NOT COVERED – Drugs that are not covered by the plan.

Code	Definition
PA	Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL	Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST	Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR	Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.

Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.

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