LUXTURNA (voretigene neparvovec-rzyl) is an
adeno-associated virus vector-based gene therapy indicated for the treatment of
patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.
Patients must have viable retinal cells as determined by
the treating physician(s).
DOSAGE AND ADMINISTRATION
For subretinal injection only.
- The recommended dose of LUXTURNA for each eye is 1.5 x 1011
vector genomes (vg), administered by subretinal injection in a total volume of
- Perform subretinal administration of LUXTURNA to each eye
on separate days within a close interval, but no fewer than 6 days apart.
- Recommend systemic oral corticosteroids equivalent to
prednisone at 1 mg/kg/day (maximum of 40 mg/day) for a total of 7 days
(starting 3 days before administration of LUXTURNA to the first eye), and followed
by tapering the dose during the following 10 days. The same corticosteroid
dosing regimen applies for the administration of LUXTURNA to the second eye. If
the corticosteroid taper following LUXTURNA administration to the first eye is
not complete three days prior to the planned LUXTURNA administration to the
second eye, then the corticosteroid regimen for the second eye replaces the
taper for the first eye.
Prepare LUXTURNA within 4 hours of administration using
sterile technique under aseptic conditions in a Class II vertical laminar flow
biological safety cabinet (BSC). Below is the list of items required for
dilution and administration syringe preparation:
- One single-dose vial of Luxturna
- Two vials of Diluent
- One 3-mL sterile syringe
- One 20G 1-inch sterile needle
- Three 1-mL sterile syringes
- Three 27G ½-inch sterile needles
- Two sterile syringe caps
- One 10-mL sterile empty glass vial
- One sterile utility drape
- One sterile plastic bag
- Two sterile labels for administration syringes
- One sterile plain label
- One sterile skin marker
Dilution Of LUXTURNA
1. Thaw one single-dose vial of LUXTURNA and two vials of
Diluent at room temperature.
2. Mix the contents of the thawed Diluent vials by gently
inverting them approximately 5 times.
3. Inspect the Diluent vials. If particulates,
cloudiness, or discoloration are visible, do not use the vial(s); new vial(s)
of Diluent should be used.
4. Obtain a 3-mL sterile syringe, a 20G 1-inch sterile
needle, and a 10-mL sterile empty glass vial.
5. Using the 3-mL syringe with 20G 1-inch needle,
transfer 2.7 mL of Diluent to the 10-mL glass vial. Dispose of the needle and
syringe in an appropriate container.
6. Mix the contents of the thawed LUXTURNA single-dose
vial by gently inverting approximately 5 times.
7. Inspect the LUXTURNA single-dose vial. If
particulates, cloudiness, or discoloration are visible, do not use the vial; a
new single-dose vial of LUXTURNA should be used.
8. Draw 0.3 mL of LUXTURNA into a 1-mL sterile syringe
with a 27G ½-inch sterile needle. (Figure 1)
Figure 1: Syringe with 0.3 mL LUXTURNA
9. Transfer 0.3 mL of LUXTURNA to the glass vial
containing 2.7 mL of Diluent from Step 5. Gently invert the 10-mL glass vial
approximately 5 times to mix the contents.
10. Using the sterile plain label and sterile skin
marker, label the 10-mL glass vial containing the diluted LUXTURNA as follows:
11. Remove all items from the BSC except the glass vial
labeled 'Diluted LUXTURNA' and the sterile skin marker.
12. Re-sanitize the BSC prior to the next steps and place
the glass vial and the sterile marker to the left side in the BSC.
Preparation Of LUXTURNA For Injection
To keep the syringes sterile, two operators are required
for transfer of the contents of the 10-mL glass vial labeled 'Diluted LUXTURNA'
into each of two sterile 1-mL syringes.
13. Place a sterile utility drape, a sterile plastic bag,
and two sterile labels into the BSC.
14. Place the sterile drape near the Primary Operator on
the right side of the sanitized BSC surface, away from the diluted LUXTURNA.
15. The Secondary Operator unwraps two 1-mL syringes, two
27G½-inch needles, and two syringe caps in the BSC, ensuring that the Primary
Operator touches only sterile surfaces while transferring the items onto the
16. The Secondary Operator changes to a new pair of
sterile gloves and stands or sits to the left of the Primary Operator. The
Secondary Operator holds the 10-mL glass vial containing the diluted LUXTURNA
Figure 2a: First Position of the Operators During
Preparation of LUXTURNA Syringes
17. The Primary Operator withdraws 0.8 mL of the diluted
LUXTURNA into a sterile 1-mL syringe using a 27G ½-inch sterile needle while
the secondary operator holds the 10-mL glass vial. After the insertion of the
needle, the Secondary Operator inverts the 10-mL glass vial enabling the
Primary Operator to withdraw 0.8 mL without touching the 10-mL glass vial
Figure 2b: Second Position of the Operators During
Preparation Of LUXTURNA Syringes
18. The Primary Operator removes the needle and affixes a
sterile cap to the sterile syringe, disposes of the needle in an appropriate
container, and attaches a sterile label to the administration syringe.
19. The Primary Operator repeats Steps 17 and 18 to
prepare a total of two administration syringes. Label the first syringe “Diluted
LUXTURNA” and label the second syringe “Back-up Diluted LUXTURNA” using the
sterile skin marker. The second syringe will serve as a backup for the surgeon
performing the subretinal administration procedure. Discard the back-up syringe
after surgery if not used.
20. Inspect both syringes. If particulates, cloudiness,
or discoloration are visible, do not use the syringe.
21. Place the syringes into the sterile plastic bag after
visual inspection and seal the bag.
22. Place the sterile plastic bag with syringes
containing diluted LUXTURNA into an appropriate secondary container (e.g., hard
plastic cooler) for delivery to the surgical suite at room temperature.
LUXTURNA should be administered in the surgical suite
under controlled aseptic conditions by a surgeon experienced in performing
intraocular surgery. In addition to the syringe containing the diluted
LUXTURNA, the following items are required for administration:
- Subretinal injection cannula with a polyamide micro tip
with an inner diameter of 41gauge.
- Extension tube made of polyvinyl chloride no longer than
6” (15.2 cm) in length and with an inner diameter no greater than 1.4mm.
Figure 3: Injection Apparatus Assembly
Follow the steps below for subretinal injection:
1. After confirming the availability of LUXTURNA, dilate
the eye and give adequate anesthesia to the patient.
2. Administer a topical broad spectrum microbiocide to
the conjunctiva, cornea and eyelids prior to surgery.
3. Inspect LUXTURNA prior to administration. If
particulates, cloudiness, or discoloration are visible, do not use the product.
4. Connect the syringe containing the diluted LUXTURNA to
the extension tube and subretinal injection cannula. To avoid excess priming
volume, the extension tube should not exceed 15.2 cm in length and 1.4 mm in
inner diameter. Inject the product slowly through the extension tube and the
subretinal injection cannula to eliminate any air bubbles.
5. Confirm the volume of product available in the syringe
for injection, by aligning the plunger tip with the line that marks 0.3 mL.
Figure 4: Volume of LUXTURNA for Injection
6. After completing a vitrectomy, identify the intended
site of administration. The subretinal injection cannula can be introduced via
pars plana. (Figure 5a)
7. Under direct visualization, place the tip of the
subretinal injection cannula in contact with the retinal surface. The
recommended site of injection is located along the superior vascular arcade, at
least 2 mm distal to the center of the fovea (Figure 5b), avoiding direct
contact with the retinal vasculature or with areas of pathologic features, such
as dense atrophy or intraretinal pigment migration. Inject a small amount of
the product slowly until an initial subretinal bleb is observed. Then inject
the remaining volume slowly until the total 0.3 mL is delivered.
Figure 5a: Subretinal injection cannula introduced via
Figure 5b: Tip of the subretinal injection cannula
placed within the recommended site of injection (surgeon’s point of view)
8. After completing the injection, remove the subretinal
injection cannula from the eye.
9. Following injection, discard all unused product.
Dispose of the back-up syringe according to local biosafety guidelines
applicable for handling and disposal of the product.
10. Perform a fluid-air exchange, carefully avoiding
fluid drainage near the retinotomy created for the subretinal injection.
11. Initiate supine head positioning immediately in the
12. Upon discharge, advise patients to rest in a supine
position as much as possible for 24 hours.
Dosage Forms And Strengths
LUXTURNA is a suspension for subretinal injection,
supplied in a 0.5-mL extractable volume in a 2-Ml single-dose vial; the
supplied concentration (5 x 1012 vg/mL) requires a 1:10 dilution prior to
administration. The Diluent is supplied in two single-use 2 mL vials.
Storage And Handling
Each carton of LUXTURNA (NDC 71394 – 415-01) contains one
single-dose vial of the LUXTURNA (NDC 71394 – 065-01, 0.5 mL extractable
volume) and two vials of Diluent (NDC 71394 – 716-01, 1.7 mL extractable volume
in each vial). LUXTURNA contains 5 x 1012 vector genomes (vg) per mL, requires
a 1:10 dilution prior to administration.
Store LUXTURNA and Diluent frozen at ≤ -65 °C.
Following thaw of the vials, store at room temperature.
Store diluted LUXTURNA at room temperature [See DOSAGE AND ADMINISTRATION].
LUXTURNA is an adeno-associated virus vector-based gene
therapy. Follow universal biohazard precautions for handling.
Manufactured by: Spark Therapeutics, Inc., 3737 Market
Street, Philadelphia, PA 19104. Revised: n/a