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Randomized Controlled Trial
. 2024 Oct 1;142(10):952-960.
doi: 10.1001/jamaophthalmol.2024.3458.

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema: The INSIGHT Randomized Clinical Trial

Susan B Bressler  1 , Abhijit Barve  2 , Prasanna C Ganapathi  3 , Katrin Beckmann  4 , Rajendra S Apte  5 , Dennis M Marcus  6 , Kristine Baumane  7 , Somesh Agarwal  8 , Piotr Oleksy  9 , David A Reichstein  10 , Sunil S Patel  11 , Jan Ernest  12 , Rozsa Dégi  13 , Vishali Gupta  14 , Genichiro Kishino  15 , Motohiro Kamei  16 , Subramanian Loganathan  17 ; INSIGHT Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema: The INSIGHT Randomized Clinical Trial

Susan B Bressler et al. JAMA Ophthalmol. .

Abstract

Importance: Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME).

Objective: To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME.

Design, setting, and participants: This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021.

Interventions: Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52.

Main outcomes and measures: The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs).

Results: A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) μm vs -124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, -3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms.

Conclusions and relevance: MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept.

Trial registration: ClinicalTrials.gov Identifier: NCT03610646.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bressler reported receiving grants from Mylan, Biocon, Boehringer Ingelheim, Genentech-Roche, Regeneron, Bayer, Biogen, Merck, and Bausch and Lomb during the conduct of the study and personal fees from Amgen outside the submitted work. Dr Barve reported being an employee of Viatris outside the submitted work. Dr Ganapathi reported being an employee of Viatris outside the submitted work. Ms Beckmann reported being an employee of Viatris outside the submitted work. Dr Apte reported serving as a consultant for Roche outside the submitted work. Dr Marcus reported receiving grants and personal fees from Annexon, Amgen, Apellis, Clearside, Coherus, Genentech-Roche, and Regeneron; personal fees from grants from Alexion, Vial, and Vantage Biosciences; and grants from Regenxbio, Boehringer Ingelheim, Gyroscope, Heidelberg, Ionis, Iveric, Opthea, Outlook, Oxurion, Rezolute, Shanghai Henlius Biotech, and Topcon during the conduct of the study. Dr Baumane reported being an employee of Riga East Clinical University Hospital outside the submitted work. Dr Agarwal reported being an employee of M & J Institute of Ophthalmology outside the submitted work. Dr Olesky reported serving as a consultant for Roche, Opthea Limited, Viatris, Polpharma, Bioeq, Thea, Intas Pharmaceuticals, Janssen, and Bayer outside the submitted work. Dr Reichstein reported receiving grants and personal fees from AiViva, Castle, Regeneron, Genentech, AiViva, Castle, Allegra outside the submitted work. Dr Patel reported receiving grants from Alcon, Apellis, Clearside, Eyepoint, Ionis, Mylan, Oculis, Opthea, Regeneron, and Samsung and grants and personal fees from Allgenesis, Genentech-Roche, and Kodiak outside the submitted work. Dr Ernest reported being an employee of Axon clinical SRO outside the submitted work. Dr Dégi reported being an employee of University of Szeged outside the submitted work. Dr Gupta reported receiving grants from Cliantha Research Limited and Ahmedabad India during the conduct of the study. Dr Kishino reported being an employee of Kozawa Eye Hospital and Diabetes Center outside the submitted work. Dr Kamei reported receiving nonfinancial support from Viatris during the conduct of the study; personal fees from Bayer Yakuhin, Boehringer Ingelheim, Chugai Pharmaceutical, Novartis Pharma, Santen Pharmaceutical, and Senju Pharmaceutical outside the submitted work. Dr Loganathan reported being an employee of Biocon Biologics Limited and having stocks and stock options of Biocon. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Disposition Chart
Figure 2.
Figure 2.. Study Design
In the figure, the dark blue rectangles indicate mandatory dosing, and the light blue rectangles indicate optional doses if prespecified criteria were met. aIn addition to the 324 participants, 1 extra participant was to be randomized for each participant meeting any of the prespecified criteria related to missed or delayed dosing or study assessments because of the COVID-19 pandemic. The maximum number of such participants was to be 70. bAdditional visits for pharmacokinetic subpopulation.
See this image and copyright information in PMC

References

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