Real-World Study Suggests Comparable Efficacy Between Biosimilar Razumab and Originator in PCV

A real-world study in India compared the ranibizumab biosimilar Razumab (Intas Pharmaceuticals) to the originator (Lucentis) in patients with polypoidal choroidal vasculopathy (PCV). The investigators said their data suggests Razumab had “comparable visual acuity outcomes” to the originator with an “adequate safety profile.”

Ranibizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF), preventing VEGF from binding with its receptors on endothelial cells, leading to inhibition of angiogenesis.

PCV is a choroidal vascular abnormality causing hemorrhages that has a high prevalence in Asian populations. Patients with PCV display increased levels of VEGF in the affected eyes, thus anti-VEGF agents have been used to treat PCV.

Razumab, the world’s first ranibizumab biosimilar. It was approved by the Drug Controller General of India in 2015 for treatment of neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusions. According to the investigators, real-world outcomes of Razumab treatment in PCV are “yet to be extensively reported.”

The retrospective chart review included both treatment-naïve and previously treated patients. Forty-one patients (41 eyes) were treated with 3 initial loading doses followed by a pro-re-nata regimen of either the reference product (21 eyes) or biosimilar (19 eyes).

The investigators recorded changes in the best-corrected visual acuity (BCVA), subretinal fluid (SRF), intraretinal fluid (IRF), SRF height, subfoveal choroidal thickness (SFCT), and safety indicators at 12, 24, and 52 weeks of therapy.

Changes in BCVA were not significantly different between groups at any time point. However, the improvement from baseline in BCVA was statistically significant in the reference product group at all visits (12, 24, 52 weeks), whereas in the biosimilar group the improvement did not reach statistical significance until 52 weeks.

SRF height and the proportions of eyes with SRF was similar between groups at baseline and all visits. There were no significant changes in SFCT and the proportion of eyes with IRF and SRF in either group, but at week 52 there was a significant reduction in SRF height in both groups. The mean (SD) number of injections was greater in the reference product group (5.41 [0.94]) than the biosimilar group (n = 4 [1.45]). Regarding safety, 1 eye in the biosimilar group developed mild anterior uveitis, which was resolved by topical corticosteroids.

The authors noted differences in baseline characteristics between groups that may have affected the results: A greater number of eyes in patients receiving the reference product were treatment-naïve, 19 of 22 compared to 2 of 19 patients receiving the biosimilar. In the biosimilar group, patients had a median of 5 anti-VEGF injections before switching to the biosimilar (at baseline), whereas the median number of anti-VEGF injections prior to baseline in the reference product group was zero. The reference product group had less SFCT than the biosimilar group at baseline, and this difference persisted through week 52. Similarly, the proportion of eyes with IRF was greater in the biosimilar group at baseline and week 12, but the difference was no longer significant by week 24.

The authors said the greater prevalence of IRF in the biosimilar group could be explained by the higher number of previously treated eyes. These patients may have had persistent IRF and/or more treatment resistant PCV.

However, they said the lack of difference in IRF at weeks 24 and 52 suggests that the biosimilar was effective at resolving the IRF. The greater number of previously treated eyes and higher proportion of IRF may have also been responsible for the observed delay in improvement in BCVA in the biosimilar group, according to the authors, as the presence of IRF influences visual outcomes. “Because the biosimilar arm has fewer treatment-naive patients than the innovator arm, the biosimilar arm may have had suboptimal outcomes,” they wrote.

The investigators acknowledged their study was limited by the differences in baseline characteristics, retrospective design, limited sample size, and lack of detail on treatments patients received prior to baseline. However, they noted the one-year follow-up as a strength and proposed further long-term prospective studies to investigate real-world outcomes of biosimilar ranibizumab treatment for managing PCV.

Reference

Soman M, Nair I, Sheth JU, Nair U. Innovator versus biosimilar ranibizumab in polypoidal choroidal vasculopathy: Real-world evidence. Ophthalmol Ther. 2022;11(3):1175-1186. doi:10.1007/s40123-022-00507-w