Summary of the safety profile In the phase 1 and phase 3 clinical studies, there were three non-serious adverse reactions of retinal deposits in three of 41 (7%) subjects that were considered to be related to voretigene neparvovec.
All three of these events were a transient appearance of asymptomatic subretinal precipitates inferior to the retinal injection site, 1-6 days after injection and resolved without sequelae. Serious adverse reactions related to the administration procedure were reported in three subjects.
One of 41 (2%) subjects reported a serious event of intraocular pressure increased (secondary to administration of depo-steroid) that was associated with treatment for endophthalmitis related to the administration procedure and resulted in optic atrophy, and one of 41 (2%) subjects reported a serious event of retinal disorder (loss of foveal function) that was assessed as related to the administration procedure.
One of 41 (2%) subjects reported a serious event of retinal detachment that was assessed as related to the administration procedure. The most common adverse reactions (incidence ≥5%) related to the administration procedure were conjunctival hyperaemia, cataract, increased intraocular pressure, retinal tear, dellen, macular hole, subretinal deposits, eye inflammation, eye irritation, eye pain and maculopathy (wrinkling on the surface of the macula).
Tabulated list of adverse reactions The adverse reactions are listed by system organ class and frequency using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data).
Table 2 Adverse reactions related to voretigene neparvovec System organ class Frequency Adverse reaction Common Retinal depositsEye disorders Not known Chorioretinal atrophy* *Includes retinal degeneration, retinal depigmentation and injection site atrophy Table 3 Adverse reactions related to administration procedure System organ class Frequency Adverse reactions Psychiatric disorders Common Anxiety Nervous system disorders Common Headache, dizziness Very common Conjunctival hyperaemia, cataract Common Retinal tear, dellen, macular hole, eye inflammation, eye irritation, eye pain, maculopathy, choroidal haemorrhage, conjunctival cyst, eye disorder, eye swelling, foreign body sensation in eyes, macular degeneration, endophthalmitis, retinal detachment, retinal disorder, retinal haemorrhage Eye disorders Not known Vitreous opacities, chorioretinal atrophy* Gastrointestinal disorders Common Nausea, vomiting, abdominal pain upper, lip pain Skin and subcutaneous tissue disorders Common Rash, swelling face Very common Intraocular pressure increased Investigations Common Electrocardiogram T wave inversion Injury, poisoning and procedural complications Common Endotracheal intubation complication, wound dehiscence *Includes retinal degeneration, retinal depigmentation and injection site atrophy Description of select adverse reactions Chorioretinal atrophy Chorioretinal atrophy has been reported as an adverse reaction during post-marketing experience and reported as progressive in some patients.
Events were temporally related to treatment and occurred in the estimated treated area of the bleb site and outside of the bleb area. Retinal atrophy may involve the fovea with possible negative effects on central vision. Following reports of chorioretinal atrophy in the post-marketing setting, a retrospective review of fundus photographs available from 39 out of 41 patients enrolled in the clinical studies was performed.
6% after year 1. 9% after year 1. 7% after year 1 in the phase 1 study. Some of these atrophies involved the fovea. 6% after year 1. 8% after year 1. In the phase 3 study, atrophies in untreated control eyes did not involve the fovea. 3% after year 1.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.