Biosimilar Bevacizumab Matches Avastin in Treating Retinopathy of Prematurity

Stivant, demonstrated similar efficacy and safety to the reference biologic Avastin (reference bevacizumab; Genentech) in treating prethreshold type 1 retinopathy of prematurity (ROP), according to a recent analysis.1

The results of the pilot study published in the Journal of Current Ophthalmology, suggest that biosimilar anti-vascular endothelial growth factor (VEGF) therapies could provide a cost-effective and accessible treatment option for premature infants at risk of severe vision loss.

ROP remains a leading cause of childhood blindness, resulting from abnormal retinal blood vessel growth in premature infants, affecting about 31.9% of infants globally, with greater prevalence in lower- and middle-income nations.2 As neonatal survival improves worldwide, the burden of ROP continues to grow, underscoring the need for affordable, safe, and effective therapies.1 Although laser photocoagulation remains a standard intervention, it can cause peripheral visual field loss and other complications. Anti-VEGF agents such as bevacizumab have emerged as effective alternatives but may be cost-prohibitive in some settings, an issue that biosimilar options can help address.

Conducted at the Khatam Eye Hospital in Mashhad, Iran, the study aimed to evaluate the noninferiority, safety, and efficacy of Stivant compared with Avastin in premature infants with bilateral prethreshold type 1 ROP. Investigators used a nonrandomized contralateral-eye design, administering Stivant to one eye and Avastin to the other. Infants were followed weekly for 4 weeks and biweekly thereafter until complete retinal vascularization.

The primary endpoint was the number of eyes achieving full vascularization without rescue laser photocoagulation. Secondary endpoints included the time between injection and full vascularization and the occurrence of ocular complications such as inflammation or infection.

A total of 44 infants (88 eyes) were included in the study, comprising 20 males and 24 females. The mean (SD) gestational age at birth was 27.6 weeks (1.8 weeks; range, 24-32 weeks), and the mean birth weight was 1737.7 g (554.9 g; range, 760-2200 g). The average age at injection was 34.5 weeks, with follow-up continuing until a mean age of 60 weeks.

Both treatments produced comparable outcomes. Thirty-nine eyes (88.4%) in each group achieved complete retinal vascularization after a single intravitreal injection. Five infants (11.3%) in both groups required bilateral rescue laser photocoagulation because of persistent or worsening disease.

The mean time to full retinal vascularization was nearly identical—25.55 weeks for Stivant and 25.46 weeks for Avastin (P = .59). Kaplan-Meier survival analysis also found no significant difference between groups (P = .928). Regression of plus disease, a clinical marker of active ROP, occurred at equivalent rates, further supporting comparable efficacy.

No ocular or systemic adverse events—including endophthalmitis, uveitis, vasculitis, or retinal detachment—were reported. “Our results demonstrated that Stivant was noninferior to Avastin in terms of efficacy and safety in treating prethreshold type I ROP,” the authors wrote. “However, due to the small sample size and pilot design, a definitive conclusion requires larger randomized studies.”

Bevacizumab has been a cornerstone in ROP management since the BEAT-ROP trial established its ability to prevent disease progression while sparing the peripheral retina. The introduction of biosimilar formulations may expand access to this therapy, particularly in regions where biologic cost is a barrier to care.

Stivant, the first bevacizumab biosimilar manufactured in Iran, has already been studied for systemic malignancies and retinal conditions such as diabetic macular edema, retinal vein occlusion, and neovascular age-related macular degeneration. Early evidence from animal models and small clinical case series supported its ophthalmic safety profile, paving the way for pediatric evaluation in ROP.

Investigators acknowledged several limitations, including the nonrandomized contralateral-eye design, which may have introduced selection bias, and the small sample size, which limited statistical power to detect rare adverse events. Functional assessments such as electroretinography and visual acuity could not be performed in the neonatal population, and long-term neurodevelopmental outcomes were not evaluated.

Despite these constraints, the findings provide meaningful preliminary data to inform future large-scale randomized controlled trials. The authors emphasized the importance of expanding research to include long-term follow-up and comprehensive visual function testing.

The study underscores the potential for biosimilars to broaden treatment access and reduce healthcare costs in pediatric ophthalmology.

“Given the growing global burden of ROP and the financial constraints of many health systems, biosimilars like Stivant could play a critical role in ensuring that effective treatments reach every infant who needs them,” the authors concluded.

References

1. Abrishami M, Golmohammadi Z, Shoeibi N, et al. Comparative efficacy and safety of biosimilar bevacizumab (Stivant) versus reference product (Avastin) in prethreshold type I retinopathy of prematurity. J Curr Ophthalmol. 2025;36(4):407-412. doi:10.4103/joco.joco_178_24

2. García H, Villasis-Keever MA, Zavala-Vargas G, Bravo-Ortiz JC, Pérez-Méndez A, Escamilla-Nùñez A. Global prevalence and severity of retinopathy of prematurity over the last four decades (1985–2021): a systematic review and meta-analysis. Arch Med Res. 2024;55(2):102967. doi:10.1016/j.arcmed.2024.102967