52-Week Data Support MYL-1701P as Aflibercept Biosimilar for DME

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Treatment with MYL-1701P, an aflibercept biosimilar, was backed by new data from the Phase 3 INSIGHT randomized clinical trial, suggesting its benefit as an alternative to reference aflibercept in eyes with diabetic macular edema (DME).¹

The 52-week INSIGHT trial was the first to assess the biosimilarity of MYL-1701P to the reference product, reporting comparable efficacy, safety, immunogenicity, and pharmacokinetics between the two aflibercept products.

“Results of the INSIGHT randomized clinical trial support use of MYL-1701P as an aflibercept biosimilar, including its use through at least 52 weeks in DME, an important indication in which aflibercept has been shown to be more effective than ranbizumab and repackaged bevacizumab at lower (worse) initial levels of visual acuity,” wrote the investigative team, led by Susan B. Bressler, MD, Wilmer Eye Institute, Johns Hopkins University School of Medicine.

First approved by the US Food and Drug Administration (FDA) in 2011, aflibercept (Eylea) has been indicated for the treatment of neovascular age-related macular degeneration (AMD), DME, and macular edema from retinal vein occlusion (RVO), diabetic retinopathy (DR), and retinopathy of prematurity (ROP).²

Biosimilar agents can represent a lower-cost alternative to originator biologic products, offering expanded access or reduced cost-related burden. Initial reports suggested reference aflibercept was more effective than ranibizumab and repackaged bevacizumab for DME treatment only, among patients with best-corrected visual acuity (BCVA) of 20/50 to 20/320.³

With MYL-1701P recently awarded FDA approval⁴, Bressler and colleagues centered on the 1-year outcomes of INSIGHT comparing the clinical similarity of MYL-1701P with the reference biologic in eyes with DME.¹

The double-masked RCT was performed at 77 US, Europe, Japan, and India centers. Eligible participants were ≥18 years old with type 1 (T1D) or type 2 diabetes (T2D) with central DME and a BCVA letter score of 73 to 38 in the study eye on an Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

Participants were randomized to formulations of intravitreal MYL-1701P 2mg or reference aflibercept every 4 weeks (Q4W), with subsequent dosing every 8 weeks (Q8W) through Week 48. Randomization was stratified by baseline BCVA (ETDRS, 73-55 vs 54-38) or geographical region (US, EU, Japan, rest of world).

INSIGHT’s primary outcome was the adjusted change in BCVA from baseline at Week 8, with an equivalence margin of –3 to +3 letters. Key secondary efficacy outcomes included the mean change in central subfield thickness (CST) at Week 8, as well as BCVA, number of injections over 52 weeks, and the incidence of ocular and nonocular adverse events (AEs) and antidrug antibodies (ADAs).

Screening took place between July 2018 and August 2020 and identified 639 participants, of which 324 were randomized at clinical centers. An additional 31 participants were randomized after a protocol amendment to lessen the effect of the COVID-19 pandemic.

Of the 355 participants (mean age, 62.2 years; 60.8% male), 179 (50.4%) were randomized to MYL-1701P and 176 (49.6%) participants to aflibercept. Upon analysis, at Week 8, the mean BCVA change was 6.60 letters versus 6.56 letters in the MYL-1701P and aflibercept cohorts, respectively.

As a result, the study met its primary outcome, with an adjusted mean difference of 0.04 letters (90% CI, –1.16 to 1.24 letters) remaining within the equivalence margin.

Regarding secondary outcomes, the mean change in CST at Week 8 was –112 µm versus –124 µm in the MYL-1701P and aflibercept cohorts, respectively (adjusted mean difference, 12 µm; 90% CI, –3 to 26 µm).

Overall, the incidence of treatment-emergent AEs was comparable between the treatment groups, including ocular (30.9% vs. 29.5%), serious ocular (0.6% vs. 1.1%), nonocular (65.2% vs. 65.3%), and serious nonocular (16.9% vs. 11.9%) events. Injection totals were comparable between groups (8.4 vs. 8.7), as were the rates of treatment-induced ADAs (2.8% vs. 5.7%).

“The efficacy data in conjunction with comparable safety, immunogenicity, and pharmacokinetics data contribute to the totality of evidence for biosimilarity of MYL-1701P with reference aflibercept,” Bressler and colleagues added.

References

1. _{Bressler SB, Barve A, Ganapathi PC, Beckmann K, et al. Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema The INSIGHT Randomized Clinical Trial. JAMA Ophthalmol. Published online September 12, 2024. doi:10.1001/jamaophthalmol.2024.3458}
2. _{Adams BS, Sorhaitz W, Stringham J. Aflibercept. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK582136/}
3. _{Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193-1203. doi:10.1056/NEJMoa1414264}
4. _{US Food and Drug Administration. FDA approves first interchangeable biosimilars to Eylea to treat macular degeneration and other eye conditions. Accessed May 31, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approvesfirst-interchangeable-biosimilars-eylea-treatmacular-degeneration-and-other-eye}