Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema
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Published:2024-09-12
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ISSN:2168-6165
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Container-title:JAMA Ophthalmology
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language:en
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Short-container-title:JAMA Ophthalmol
Author:
Bressler Susan B.1, Barve Abhijit2, Ganapathi Prasanna C.3, Beckmann Katrin4, Apte Rajendra S.5, Marcus Dennis M.6, Baumane Kristine7, Agarwal Somesh8, Oleksy Piotr9, Reichstein David A.10, Patel Sunil S.11, Ernest Jan12, Dégi Rozsa13, Gupta Vishali14, Kishino Genichiro15, Kamei Motohiro16, Loganathan Subramanian17, , Chaudhry Nauman A18, Reichstein David A18, Tabassian Ali R18, Fine Howard F18, Sjaarda Raymond N18, Marcus Dennis M18, Barakat Mark R18, Dugel, Pravin U18, Eichenbaum David A18, Dessouki Amr L18, Berger Adam S18, Angle Bryan N18, Chang Margaret A18, Patel Sunil S18, Brown David M18, Thach Allen B18, Baker Carl W18, Gordon Alan J18, Mansour Sam E18, Fox Gregory M18, Alfaro Daniel Virgil18, Davies John B18, Ghorayeb Ghassan R18, Stoller Glenn L18, Johnson Thomas Mark18, Nemcansky Jan18, Rehak Jiri18, Studnicka Jan18, Ernest Jan18, Korda Vladimir18, Veith Miroslav18, Krzyzanek Daniel18, Kalvodova Bohdana18, Stodulka Pavel18, Feltgen Nicolas18, PD Katrin Lorenz18, Grisanti Salvatore18, Gamulescu Maria- Andreea18, Kellner Ulrich18, Sekundo Walter18, Dahlke Claudia18, Zeitz Oliver18, Baumane Kristine18, Laganovska Guna18, Ozolina Signe18, Vajas Attila18, Seres Andras18, Tsorbatzoglou Alexis18, Radnoti Judit18, Kiss Katalin K18, Gombos Katalin18, Degi Rozsa18, Varsanyi Balazs18, Kerenyi Agnes18, Noge Sumiyo18, Muramatsu Tomoyuki18, Kaga Tatsushi18, Oh Hideyasu18, Watanabe Miki18, Oshima Yuji18, Fujita Hideaki18, Kishino Genichiro18, Hanemoto Tsukasa18, Murata Koji18, Kitaoka Takashi18, Saito Isao18, Tanabe Teruyo18, Ebihara Nobuyuki18, Imaizumi Hiroko18, Ishii Kiyoshi18, Kamei Motohiro18, Furuta Minoru18, Ojima Akira18, Sawada Osamu18, Kawasaki Tsutomu18, Otake Hiroshi18, Doi Norihito18, Abe, Keitetsu18, Matsuda Satoshi18, Kobayashi Namie18, Yoshizumi Yuki18, Budzinskaya Maria18, Lebedev Oleg18, Eremina Alena18, Zolotarev Andrey18, Izmaylov Alekxandr18, Samoylov Alexandr18, Astakhov Sergei18, Astakhov Yury18, Shkvorchenko Dmitry18, Narayanan Raja18, Agarwal Komal18, Rahul Shroff18, Natesh Sribhargava18, Gupta Vishali18, Panchal Bhavik18, Kaza Hrishikesh18, K Minija C18, Agrawal Virendra18, Elhence Arti18, Behera Umesh Chandra18, Raj Lional18, Mazumdar Shahana18, Kannan Naresh Babu18, Yadav Naresh Kumar18, Vohra Rajpal18, Aggarwal Somesh18, Sonawane Ashwini18, Saravanan Veerappan R18, Chauhan Rohan R18, Fluder Ewa Maria18, Nawrocki Jerzy18, Wylegala Edward18, Zalewski Dominik18, Oleksy Piotr18, Borcz Emilia18
Affiliation:
1. Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 2. Viatris Inc, Canonsburg, Pennsylvania 3. Viatris, Bangalore, India 4. Viatris Healthcare GmbH, Hannover, Germany 5. Washington University School of Medicine, St Louis, Missouri 6. Southeast Retina Center Ophthalmology Department, Augusta, Georgia 7. Riga East Clinical University Hospital, Riga, Latvia 8. M & J Institute of Ophthalmology–BJ Medical College, Gujarat, India 9. Centrum Medyczne UNO-MED, Tarnow, Poland 10. Tennessee Retina, Nashville 11. Retina Research Institute of Texas, Abilene 12. Axon Clinical SRO, Praha 5-Smíchov, Czech Republic 13. University of Szeged, Koranyi Favor 10-11, Szeged, Hungary 14. Postgraduate Institute of Medical Education & Research–Advanced Eye Centre, Punjab, India 15. Kozawa Eye Hospital and Diabetes Center, Ibaraki, Japan 16. Aichi Medical University Hospital, Aichi, Japan 17. Clinical Development & Medical Affairs Department, Biocon Biologics Ltd, Bangalore, Karnataka, India 18. for the INSIGHT Study Group
Abstract
ImportanceBiosimilars 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).ObjectiveTo compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME.Design, Setting, and ParticipantsThis 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.InterventionsFormulations 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 MeasuresThe 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).ResultsA 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 RelevanceMYL-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 RegistrationClinicalTrials.gov Identifier: NCT03610646
Publisher
American Medical Association (AMA)
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