Real-world Study of Reference vs Biosimilar Ranibizumab for Treatment of Diabetic Macular Edema in India

A retrospective, real world study found similar effectiveness and safety of biosimilar ranibizumab (Razumab; Intas) and its reference product (Accentrix; Novartis) in patients with diabetic macular edema (DME) in a network of eye care centers and teaching hospitals in eastern India.

The authors noted DME “is one of the leading causes of visual impairment globally and the increasing prevalence of diabetes means that there will be an exponential rise in the number of patients with DME.” They also said that the treatment of DME “has seen paradigm shifts in the

last decade” because of the use of anti-vascular endothelial growth factor (VEGF) therapies, such as ranibizumab.

Ranibizumab is an anti-VEGF antibody fragment, delivered via intravitreal injection to treat ophthalmic conditions such as neovascular (wet) age-related macular degeneration, DME, and myopic choroidal neovascularization. In the United States, Accentrix is marketed under the name Lucentis and is commercialized by Genentech.

The authors commented that although reference ranibizumab “is available at a substantially reduced cost in India,” multiple injections “can be cost-prohibitive.” The biosimilar Razumab, the world’s first ranibizumab biosimilar, was approved by the drug controller general of India (DGCI) in 2015. According to the authors, the institutions involved in the study have been “increasingly” adopting the biosimilar in recent years “as confidence in this molecule grows; currently, more than half of all our patients receive [biosimilar ranibizumab].”

In the US, Samsung Bioepis and Biogen’s Byooviz was the first ranibizumab biosimilar to gain FDA approval in 2021. Byooviz was approved by Canadian regulatory authorities in early 2022.

The researchers analyzed electronic health records of patients with DME at their network of eye care centers and hospitals who received at least 3 injections of the originator or biosimilar plus 6 months of follow-up in their pro re nata (PRN) treatment protocol. They found 333 eyes that met their inclusion criteria and were able to be matched for similar follow-up duration, of which 264 were treated with the originator and 69 were treated with the biosimilar. Baseline characteristics, duration of follow-up, and mean number of injections were similar in the reference product and biosimilar groups.

The primary outcome of the study was a comparison of improvement in the best corrected visual acuity (BCVA) at 6 months between the reference product and biosimilar. Overall, the mean BCVA improved from baseline to 3 months, then remained stable at 6 months and 1 year, with a mean improvement of 0.24 (+/- 0.39) logarithm of minimum angle of resolution (logMAR) units at 1 year among all patients. The researchers found no differences in BCVA between groups at any time point.

Another effectiveness outcome the researchers analyzed was central macular thickness (CMT). The overall mean CMT improved from baseline to 1 month and 1 month to 3 months, then remained stable at 6 months and 1 year. Similar to BCVA, no differences were detected between groups at any time point. The mean reduction in CMT was 120 (+/- 196) μm in the patients treated with the reference product and 105 (+/- 187) μm in the patients treated with the biosimilar. The authors noted, “macular edema also decreased over time and equally well in both groups.”

The researchers reported no adverse events, saying “none of the eyes included in this

study experienced any adverse reactions such as intraocular inflammation or endophthalmitis,

and none of the patients suffered any drug-related systemic adverse events such as thromboembolism, myocardial infarction, or stroke during the follow-up period.”

In the study, no differences in visual and anatomical outcomes were found between treatment-naive patients with DME who received the originator vs the biosimilar ranibizumab. Although “lack of comparative studies with a significant period of follow-up with the innovator molecule has led to skepticism amongst physicians and has prevented widespread adoption,” the authors wrote, “our results are encouraging and should alleviate concerns about efficacy of the biosimilar for management of DME.”

Reference

Chakraborty D, Sengupta S, Mondal S, et al. Comparison of innovator vs. biosimilar ranibizumab in treating diabetic macular edema: A multicenter retrospective study. Ophthalmol Ther. 2022;11(2):629-638. doi:10.1007/s40123-022-00463-5