LUXTURNA(voretigene neparvovec-rzyl)intraocular suspension forsubretinal injection(六)
ubjects was 17 years ranging
from 4 to 44 years. Of the 41 subjects, 25 (61%) were pediatric subjects under 18 years of age, and 23 (56%)were females.
Twenty-seven (27/41, 66%) subjects had ocular adverse reactions that involved 46 injected eyes (46/81, 57%).
Adverse reactions among all subjects in Studies 1 and 2 are described in Table 1. Adverse reactions may have
been related to voretigene neparvovec-rzyl, the subretinal injection procedure, the concomitant use ofcorticosteroids, or a combination of these procedures and products.
Table 1. Ocular Adverse Reactions Following Treatment with LUXTURNA (N=41)
Adverse Reactions Subjects n=41 Treated Eyes n=81
Any ocular adverse reaction 27 (66%) 46 (57%)
Conjunctival hyperemia 9 (22%) 9 (11%)
Cataract 8 (20%) 15 (19%)
Increased intraocular pressure 6 (15%) 8 (10%)
Retinal tear 4 (10%) 4 (5%)
Dellen (thinning of the corneal stroma) 3 (7%) 3 (4%)
Macular hole 3 (7%) 3 (4%)
Subretinal deposits* 3 (7%) 3 (4%)
Eye inflammation 2 (5%) 4 (5%)
Eye irritation 2 (5%) 2 (2%)
Eye pain 2 (5%) 2 (2%)
Maculopathy (wrinkling on the surface
of the macula) 2 (5%) 3 (4%)
Foveal thinning and loss of foveal
function 1 (2%) 2 (2%)
Endophthalmitis 1 (2%) 1 (1%)
Foveal dehiscence (separation of the
retinal layers in the center of the macula) 1 (2%) 1 (1%)
Retinal hemorrhage 1 (2%) 1 (1%)
*Transient appearance of asymptomatic subretinal precipitates inferior to the retinal injection site 1-6 days after injectionImmunogenicity
At all doses of LUXTURNA eva luated in Studies 1 and 2, immune reactions and extra-ocular exposure weremild. In Study 1 (n=12), the interval between the subretinal injections into the two eyes ranged from 1.7 to 4.6years. In Study 2, the interval between the subretinal injections into the two eyes ranged from 7 to 14 days. No
subject had a clinically significant cytotoxic T-cell response to either AAV2 or RPE65.
Subjects received systemic corticosteroids before and after subretinal injection of LUXTURNA to each eye.
The corticosteroids may have decreased the potential immune reaction to either vector capsid (adeno-associatedvirus serotype 2 [AAV2] vector) or transgene product (retinal pigment epithelial 65 kDa protein [RPE65]).
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Adequate and well-controlled studies with LUXTURNA have not been conducted in pregnant women. Animalreproductive studies have not been conducted with LUXTURNA. In the U.S. general population, the estimatedbackground risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
8.2 Lactation
Risk Summary
There is no information regarding the presence of LUXTURNA in human milk, the effects on the breastfedinfant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LUXTURNA and any potential adverse effects on thebreastfed infant from LUXTURNA.
8.3 Females and Males of Reproductive Potential
No nonclinical or clinical studies were performed to eva luate the effect of LUXTURNA on fertility.
8.4 Pediatric Use
Treatment with LUXTURNA is not recommended for patients younger than 12 months of age, because theretinal cells are still undergoing cell proliferation, and LUXTURNA would potentially be diluted or lost duringcell proliferation.
The safety and efficacy of LUXTURNA have been established in pediatric pat |
