Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema
Authors: Bressler Susan B. , Barve Abhijit , Ganapathi Prasanna C. , Beckmann Katrin , Apte Rajendra S. , Marcus Dennis M. , Baumane Kristine , Agarwal Somesh , Oleksy Piotr , Reichstein David A. , Patel Sunil S. , Ernest Jan , Dégi Rozsa , Gupta Vishali , Kishino Genichiro , Kamei Motohiro , Loganathan Subramanian ,   INSIGHT Study Group, Chaudhry Nauman A , Reichstein David A , Tabassian Ali R , Fine Howard F , Sjaarda Raymond N , Marcus Dennis M , Barakat Mark R , Dugel, Pravin U , Eichenbaum David A , Dessouki Amr L , Berger Adam S , Angle Bryan N , Chang Margaret A , Patel Sunil S , Brown David M , Thach Allen B , Baker Carl W , Gordon Alan J , Mansour Sam E , Fox Gregory M , Alfaro Daniel Virgil , Davies John B , Ghorayeb Ghassan R , Stoller Glenn L , Johnson Thomas Mark , Nemcansky Jan , Rehak Jiri , Studnicka Jan , Ernest Jan , Korda Vladimir , Veith Miroslav , Krzyzanek Daniel , Kalvodova Bohdana , Stodulka Pavel , Feltgen Nicolas , PD Katrin Lorenz , Grisanti Salvatore , Gamulescu Maria- Andreea , Kellner Ulrich , Sekundo Walter , Dahlke Claudia , Zeitz Oliver , Baumane Kristine , Laganovska Guna , Ozolina Signe , Vajas Attila , Seres Andras , Tsorbatzoglou Alexis , Radnoti Judit , Kiss Katalin K , Gombos Katalin , Degi Rozsa , Varsanyi Balazs , Kerenyi Agnes , Noge Sumiyo , Muramatsu Tomoyuki , Kaga Tatsushi , Oh Hideyasu , Watanabe Miki , Oshima Yuji , Fujita Hideaki , Kishino Genichiro , Hanemoto Tsukasa , Murata Koji , Kitaoka Takashi , Saito Isao , Tanabe Teruyo , Ebihara Nobuyuki , Imaizumi Hiroko , Ishii Kiyoshi , Kamei Motohiro , Furuta Minoru , Ojima Akira , Sawada Osamu , Kawasaki Tsutomu , Otake Hiroshi , Doi Norihito , Abe, Keitetsu , Matsuda Satoshi , Kobayashi Namie , Yoshizumi Yuki , Budzinskaya Maria , Lebedev Oleg , Eremina Alena , Zolotarev Andrey , Izmaylov Alekxandr , Samoylov Alexandr , Astakhov Sergei , Astakhov Yury , Shkvorchenko Dmitry , Narayanan Raja , Agarwal Komal , Rahul Shroff , Natesh Sribhargava , Gupta Vishali , Panchal Bhavik , Kaza Hrishikesh , K Minija C , Agrawal Virendra , Elhence Arti , Behera Umesh Chandra , Raj Lional , Mazumdar Shahana , Kannan Naresh Babu , Yadav Naresh Kumar , Vohra Rajpal , Aggarwal Somesh , Sonawane Ashwini , Saravanan Veerappan R , Chauhan Rohan R , Fluder Ewa Maria , Nawrocki Jerzy , Wylegala Edward , Zalewski Dominik , Oleksy Piotr , Borcz Emilia 
Published: September 2024

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