Aflibercept Biosimilar MYL-1701P Provides Equivalence in DME Therapy

The aflibercept biosimilar MYL-1701P demonstrated equivalent efficacy and comparable safety to reference aflibercept for treating diabetic macular edema (DME), according to a 52-week randomized clinical trial.¹

The findings, published in JAMA Ophtalmology, support the potential for biosimilars to lower treatment costs, improve access to effective therapies, and reduce the economic burden on health care systems. This is particularly important in DME, where aflibercept has been shown to outperform other treatments in patients with lower baseline visual acuity.

DME is caused by fluid buildup in the retina due to leaky and damaged blood vessels, often linked to diabetic retinopathy. It stems from microvascular changes and hypoxia, which stimulate VEGF production, increasing vessel permeability and promoting edema. In 2010, approximately 746,000 individuals in the US aged 40 and older (3.8% of those with diabetes) were affected by DME.² Globally, the prevalence of diabetes has grown significantly, contributing to over 150 million DME cases worldwide, reflecting the impact of rising diabetes rates.³

This study was a prospective, double-masked, multicenter, parallel-group, active-controlled clinical trial conducted at 77 centers across 9 countries from August 2018 to September 2021. It compared MYL-1701P and aflibercept in patients with DME, with a 4-week screening, 48-week treatment phase, and 4-week follow-up.

Participants were randomly assigned to receive either MYL-1701P or aflibercept via intravitreal injections. The primary outcome was mean change in best-corrected visual acuity (BCVA) at week 8, with secondary outcomes of changes in central subfield thickness (CST) and the proportion of participants gaining 15 or more BCVA letters. Safety, immunogenicity (antidrug antibodies [ADA]), and pharmacokinetics were also assessed.

Of the 639 participants screened, 355 were randomized to MYL-1701P (n = 179) or reference aflibercept (n = 176). The mean age was 62.2 years, and 64.2% were White. Completion rates were high, with 97.2% finishing the week 8 visit and 89.9% completing week 52.

In terms of clinical efficacy, the primary outcome showed nearly identical results for MYL-1701P and aflibercept, with changes in BCVA of 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups, respectively, meeting the equivalence margin. Secondary outcomes, including changes in CST, were also comparable between the groups, with the adjusted mean difference in CST at week 8 being 11 μm. At week 52, the cumulative number of injections was similar (n = 8.4 for MYL-1701P vs 8.7 for aflibercept), and the proportions of participants gaining 5 or more, 10 or more, or 15 letters or more were comparable.

Regarding safety, the incidence of nonocular treatment-emergent adverse events (TEAEs) was 65.2% for MYL-1701P and 65.3% for aflibercept, with most being mild or moderate. Serious nonocular TEAEs were slightly more frequent in the MYL-1701P group (16.9% vs 11.9%). The incidence of ocular TEAEs was similar between groups, with no cases of ocular inflammation or endophthalmitis in the MYL-1701P group. A total of 6 deaths occurred during the study (n = 2 in MYL-1701P and 4 in aflibercept), all deemed unrelated to the study.

Pharmacokinetic data revealed comparable plasma concentrations for both treatments, with no evidence of drug accumulation. The incidence of ADAs was low and similar between the groups, with no neutralizing antibodies found in the MYL-1701P group and 1 case in the aflibercept group.

Overall, MYL-1701P was found to be comparable to aflibercept in terms of both efficacy and safety for the treatment of diabetic macular edema.

Despite positive findings, the study had limitations, including a lack of racial diversity, with most participants being Asian or White and minimal African American representation. The trial was also conducted during the COVID-19 pandemic, leading to an adjusted sample size. A small percentage of participants missed doses, but sensitivity analyses indicated no impact on the equivalence results.

References

1. Bressler SB, Barve A, Ganapathi PC, et al. Aflibercept biosimilar MYL-1701P vs reference aflibercept in diabetic macular edema. JAMA Ophthalmol. 2024;142(10):952-960. doi:10.1001/jamaophthalmol.2024.3458

2. Varma R, Bressler NM, Doan QV, et al. Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol. 2024;132(11):1334-1340. doi:10.1001/jamaophthalmol.2014.2854

3. Musat O, Cernat C, Labib M, et al. Diabetic macular edema. Rom J Ophthalmol. 2015;59(3):133-136. https://pmc.ncbi.nlm.nih.gov/articles/PMC5712956/#R1