Study: Ranibizumab Biosimilar Found Safe, Effective in Infants With Retinopathy

Razumab, a ranibizumab biosimilar developed by Intas Pharmaceuticals, was found to be safe and effective in infant patients with retinopathy of prematurity (ROP), according to data from a retrospective study from India.

The study is the first to assess clinical outcomes associated with the use of Razumab in this population. Razumab references Lucentis (ranibizumab), also known as Accentrix in India. The biosimilar has been on the Indian market since 2015 and has produced positive outcomes in patients with diabetic macular edema and neovascular age-related macular degeneration. However, its use in ROP has not been studied before.

In many low- and middle-income countries, Lucentis is cost-prohibitive for the majority of the population and biosimilars like Razumab offer a way to address the growing need for ranibizumab treatment globally.

The researchers conducted their analysis at the ophthalmology department of a government medical college in Western India. Data from 118 eyes of 59 babies with stage 3 or higher ROP, either in zone 1 or 2 posterior (APROP), were analyzed. After consent was obtained from the parents and they agreed to a minimum follow-up of up to 4 months of age, the infants underwent intravitreal injection of Razumab (0.25 mg/0.025 mL).

APROP is considered to be the most severe and virulent form of ROP. It involves the posterior pole that can quickly progress to retinal detachment if left unchecked. The use of anti-vascular endothelial growth factor agents, such as bevacizumab and ranibizumab, are commonly used to manage APROP worldwide.

The median gestational age of the babies was 30 weeks and 52% of them were boys. The median birth weight was 1250 mg and the median time of first presentation was 29 days after birth. The participants spent an average (SD) of 23.4 (14.7) days in the neonatal intensive care union (NICU). Common risk factors found in the babies included oxygen administration (95%), respiratory distress syndrome (34%), and sepsis (10%). Additionally, APROP was found in 28 eyes (24%), stage 3 ROP was observed in zone 1 in another 28 eyes (24%), and stage 3 ROP in zone 2 was seen in the remaining 62 eyes (52%).

Complete resolution of ROP was seen in 22 eyes (19%) at an average of 55 days post-injection, and 42 eyes (35%) showed a recurrence in neovascularization for which they received repeat injection at a median of 51 days post-injection. Overall, 45% of eyes did not develop recurrence or complete vascularization after 6 weeks and required laser treatment to the residual avascular retina. None of the infants died or experienced notable treatment-related adverse events. The most significant risk factor for recurrence was APROP.

The authors said that their results were similar to those presented a longitudinal national surveillance study of infants treated with ranibizumab monotherapy for ROP from the United Kingdom. The results were also similar to other studies assessing ranibizumab monotherapy in infants.

“From our own experience and supporting literature, we recommend close monitoring of infants especially during the 6–8‐week period after the first ranibizumab injection, since this appears to be the peak time for recurrence that requires retreatment. Additionally, eyes with APROP are 2.5 times more prone to develop recurrence and hence need closer monitoring,” the authors wrote.

Additionally, the researchers noted that although half of the eyes in the cohort did not reach complete vascularization after 6 weeks post-administration or required laser treatment, they believe that the amount of laser required was significantly reduced after ranibizumab injection rather than if laser treatment was conducted in the first place, potentially resulting in lower degrees of myopia in the patients.

“We also believe that at six weeks post injection, it is possible to restrain infants and perform laser safely under sedation while it may require general anesthesia at later times to perform laser safely. However, timing of laser to residual retina without disease recurrence or reactivation requires further study.”

The main drawback of the study was that a head-to-head comparison between the biosimilar and the originator was not conducted. However, the large sample side and use of widefield retinal imaging to monitor patients were considered strengths.

“Given the advantages of its cost‐benefit as well as comparable efficacy, Razumab may be safely used in managing ROP by retina physicians globally. With widespread use, more data would be available to corroborate our findings,” they concluded.