EYLEA (aflibercept) - Retinopathy of prematurity (ROP)

The clinical benefit of EYLEA 40 mg/mL (aflibercept) solution for injection in pre-filled syringe in the treatment of retinopathy of prematurity is low only in the following situations:

• in highly active forms of the disease (aggressive posterior ROP),
• in the event of extensive zone I disease,
• if it is impossible to perform laser therapy or general anaesthesia.

Considering:

• the results of the FIREFLEYE study demonstrating high response percentages (absence of active ROP and unfavourable structural outcomes) at week 24 with aflibercept and similar to those in the laser photocoagulation group (85.5% versus 82.1%), in 121 preterm infants with retinopathy;
• the results of the FIREFLEYE NEXT extension study in infants at 2 years of age, demonstrating maintenance of the clinical response in the aflibercept and laser groups;
• the medical need partially met by laser photocoagulation, which can sometimes be difficult to perform (in the operating theatre, under general anaesthesia that can sometimes last several hours and by a trained ophthalmologist) or even impossible (particularly in preterm infants who are too unstable to undergo general anaesthesia or in the event of poor visualisation of the eye fundus) and is associated with short and long-term complications impairing vision (reduction in peripheral field of vision, myopia and strabismus);
• the advantages of anti-VEGF injection compared to laser photocoagulation since it is possible to administer the injection at the patient’s bedside, under shorter and less deep anaesthesia, without the need to move them to the operating theatre or an expert centre;

but considering:

• the lack of formal demonstration of the non-inferiority of aflibercept compared to laser photocoagulation in the FIREFLEYE study;
• as well as in the BUTERFLEYE study conducted in the USA, with an assessment at week 52 with the same primary efficacy endpoint;
• that only the “summary of evidence” study, the aim of which was to compare the efficacy results observed with aflibercept in the FIREFLEYE study with those in the laser photocoagulation group, increasing the number of patients in the latter group by adding the results of two historic studies, suggests this non-inferiority;
• uncertainties concerning the long-term efficacy (risk of late recurrence) and safety (consequences of systemic absorption of anti-VEGF therapies in a vulnerable population, particularly on psychomotor development) and the absence of data beyond the age of 2 years;

the Committee deems that EYLEA 40 mg/mL (aflibercept) solution for injection in pre-filled syringe provides no clinical added value (CAV V) in the current care pathway for retinopathy of prematurity.