Biosimilar ranibizumab measures up to original for nAMD

In the treatment of patients with neovascular age-related macular degeneration (nAMD), the biosimilar FYB201 appears to have similar efficacy, safety, and immunogenicity as ranibizumab, as shown in the results of a phase III study.

“Improvement in best corrected visual acuity (BCVA) occurred in both treatment groups from the first administration of drug (ie, observed from week 4 onward), with equivalent improvement in BCVA shown for FYB201 versus reference ranibizumab at week 8, the primary study endpoint,” according to the investigators.

“The assessment at week 8 was endorsed by regulatory authorities because it is in the linear, steep part of the dose-response curve. Therefore, it is within the most sensitive timepoint to detect any potential efficacy differences between the reference product and FYB201,” they added.

Patients in both treatment groups achieved comparable reductions in foveal center point (FCP) and foveal central subfield (FCS) retinal thickness, as well as total lesion area. Likewise, there were no differences in the proportion of patients with active choroidal neovascularization (CNV) leakage and those with a fluid-free macula.

“Both drugs were well tolerated, with no differences in immunogenicity and safety profile. There were no obvious safety concerns, with the safety profile of FYB201 consistent with the established safety of the reference product,” the investigators said.

The trial included 477 patients (median age 76 years, 56.4 percent female), of whom 238 received FYB201 and 239 ranibizumab 0.5 mg, administered via intravitreal injection in the study eye every 4 weeks. These patients were enrolled from sites in Austria, Czech Republic, France, Germany, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, and the UK.

At week 8, mean BCVA increased by 5.1 and 5.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters with the biosimilar and the reference, respectively. The analysis of covariance (ANCOVA) least squares mean difference was within the predefined equivalence margin (–0.4 ETDRS letters, 90 percent confidence interval, –1.6 to 0.9). [Ophthalmology 2021;doi:10.1016/j.ophtha.2021.04.031]

Overall, the frequency and type of adverse events (AEs) were similar in the treatment groups. The most frequent drug-related ocular AEs in the FYB201 and ranibizumab groups, respectively, were cataract (0.0 percent and 2.1 percent), retinal pigment epithelium tear (0.4 percent and 1.3 percent), reduced visual acuity (0.0 percent and 1.3 percent), and punctate keratitis (0.0 percent and 0.8 percent), among others.

The most common systemic AEs were nAMD in the fellow eye (7.6 percent and 8.8 percent), nasopharyngitis (5.0 percent and 6.7 percent), hypertension (1.3 percent and 5.9 percent), and increased C-reactive protein level (4.2 percent and 2.1 percent).

“Over the past 10 years, no safety concerns have been identified with regard to differences in the nature, severity, or frequency of adverse effects between biosimilar medicines and their reference medicines. Biosimilars have also been shown to increase price competition between pharmaceutical products,” according to the investigators. [tinyurl.com/yfeqk5ry; tinyurl.com/y4kfsmza]

“To date, the use of biosimilars in ophthalmology has been limited. Although a version of ranibizumab is marketed in India, biologic copies marketed in some countries may not have gone through the rigorous biosimilar approval process required in the US, Europe, and elsewhere. However, another consideration in nAMD is the off-label use of bevacizumab; though is not approved for ophthalmological use, it is still widely used,” they said.

Alarm has been raised over the safety of off-label bevacizumab, specifically the potential for compounding-related endophthalmitis. Nevertheless, clinical trials and reviews have revealed no significant differences in safety or efficacy in comparison with bevacizumab and ranibizumab. [Br J Ophthalmol 2013;97:266-271; Ophthalmology 2015;122:146-152; Ophthalmology 2016;123:70-77.e1; Cochrane Database Syst Rev 2014;9:Cd011230]

“As such, it will be of interest to see how potential uptake of biosimilar ranibizumab may be influenced by the availability of a low-cost widely used but unlicensed alternative,” the investigators said. “However, it is expected that the availability of biosimilars for ranibizumab may increase access to treatment.”