Safety, Efficacy of Ranibizumab Biosimilars Appear Similar to Reference Product

Carl C. Awh, MD

Credit: Retina Fellows Forum

A new analysis suggests initial experiences with 2 ranibizumab biosimilars, ranibizumab-nuna (Byooviz) and ranibizumab-eqrn (Cimerli), revealed no unexpected adverse outcomes in treated eyes, while clinical efficacy appeared equivalent to the reference product (Lucentis).¹

The study, presented at the American Society of Retina Specialists (ASRS) 41st Annual Meeting, was comprised of more than 5,000 eyes treated with either biosimilar agent at 16 retina practices across the United States.

“Our initial experience with ranibizumab biosimilar agents revealed no unexpected adverse outcomes,” said Carl C. Awh, MD, president, Tennessee Retina. “The clinical efficacy of the biosimilar agents seems equivalent to ranibizumab. We will continue to evaluate and report.”

The patent for ranibizumab expired in 2020. The US Food and Drug Administration (FDA) has since approved 2 biosimilar ranibizumab, ranibizumab-nuna (Byooviz) in September 2021² and ranibizumab-eqrn (Cimerli) in August 2022.³ Each approval was based on clinical trials of approximately 700 patients, showing equivalent efficacy and safety of the biosimilar to the reference product.

The retrospective, non-randomized, consecutive case series identified eyes receiving ranibizumab biosimilars in a large consortium of retina practices across the US, with a common electronic health record platform. The analysis identified patients with at least 28 days of follow-up following the first injection of the ranibizumab biosimilar.

Investigators collected data on diagnosis, number of prior anti-VEGF injections, and visual acuity. Additionally, they captured new findings on the anterior chamber or vitreous cells, endophthalmitis, vasculitis, or other adverse events.

Overall, 5085 eligible eyes of 3964 patients (mean age, 77.8 years; 38.62% male) with ≥28 days of follow-up beginning in September 2021 were identified for analysis. Of these eyes, 3957 were previously treated with a different anti-VEGF, with a mean number of prior injections of 5.6. The mean number of additional biosimilar injections following 1st treatment was 1.65.

A total of 13,459 injections of the 2 biosimilar ranibizumab agents were administered and included in the analysis: 5049 injections for ranibizumab-nuna and 8410 injections for ranibizumab-eqrn. The investigative team found no statistically significant difference in visual acuity at 1-, 2-, and 3 months post-injection (P = .12).

At baseline, the mean VA was 0.56 ±0.56 logMAR. The mean VA of the 5085 examined at 1-, 2-, and 3-months post-baseline was 0.56 logMAR, 0.57 logMAR, and 0.56 logMAR, respectively.

Safety analyses showed 9 cases (0.067%) of minimal anterior chamber or vitreous cells without vision loss. There were no cases of retinal vasculitis and no cases of inflammation presumed secondary to a drug reaction. Investigators, however, identified 3 cases (0.022%) of presumed bacterial endophthalmitis.

The data showed 1 eye decreased from 20/40 to 20/200 and 1 eye returned to 20/30 baseline, but both were able to be re-treated with ranibizumab biosimilar without subsequent complications. Another eye experienced a decrease to hand-motion vision, with dense vitreous debris, but the patient was medically unable to undergo a vitrectomy. Investigators noted the fellow eye received the same biosimilar agent and did not experience the same complications.

Overall, the endophthalmitis rate was 1/4486 (0.022%). The rate for ranibizumab-nuna was 1/2525 (0.04%) and the rate for ranibizumab-eqrn was 1/8410 (0.01%). The cases of endophthalmitis occurred in the first 900 injections (1/300), but there were no subsequent cases of endophthalmitis in the next 12,500 injections.

“The [ranibizumab-nuna] rate was somewhat higher than the [ranibizumab-eqrn] rate, but I emphasize our sample size is inadequate to determine definitive rates,” Awh said. “This is a reminder of the Law of Small Numbers.”

References

1. Efficacy and Safety of Biosimilar Ranibizumab-nuna and Ranibizumab-eqrn in Clinical Use by a Consortium of Retina Practices. Paper presentation at the American Society of Retina Specialists 41st Annual Meeting. July 28 - August 1.
2. Iapoce C. FDA approves ranibizumab biosimilar for treatment of retinal vascular disorders. HCP Live. September 20, 2021. Accessed August 18, 2023. https://www.hcplive.com/view/fda-approves-ranibizumab-biosimilar-treatment-retinal-vascular-disorders.
3. Iapoce C. FDA approves ranibizumab-eqrn as first interchangeable biosimilar to ranibizumab. HCP Live. August 3, 2022. Accessed August 18, 2023. https://www.hcplive.com/view/fda-approves-ranibizumab-eqrn-first-biosimilar-ranibizumab.