Comparative Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea® in Subjects With Diabetic Macular Edema (DME)

Three hundred and twenty-four (324) eligible adult subjects with diabetes mellitus with central DME involvement to be randomized 1:1 to intravitreal treatment with MYL-1701P or Eylea®. Subjects to receive the assigned treatment until Week 48.

All subjects to return to clinic every 4 weeks to assess safety, efficacy and to guide treatment. Additional visits allowed during the study as specified in the study schedule for safety and pharmacokinetic evaluation.

Pharmacokinetics (PK) and Immunogenicity to be assessed in the subjects participating in the study.

• MYL-1701P (Drug): Subjects will receive intravitreal injections of MYL-1701P throughout the 52-week treatment period, with the last dose at 48 weeks. The additional doses may be administered in accordance with the protocol.
• Eylea (Drug): Subjects will receive intravitreal injections of Eylea throughout the 52-week treatment period, with the last dose at 48 weeks. The additional doses may be administered in accordance with the protocol.

Primary outcomes

• Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8 [Baseline and 8 weeks]: Mean change from baseline in BCVA as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8. Best Corrected Visual Acuity (BCVA) is measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the ETDRS chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.

Secondary outcomes

• The Mean Change From Baseline in Central Retinal Thickness (CRT) [From baseline to week 52]: The mean change from baseline in Central Retinal Thickness as determined by Spectral domain- Optical coherence tomography (SD-OCT) over time
• The Mean Change in BCVA [From baseline to week 52]: Mean change from baseline in BCVA as assessed by ETDRS letters over time. Best Corrected Visual Acuity (BCVA) is measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the ETDRS chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening
• Number of Subjects Who Gained ≥15 Letters From Baseline in BCVA [From baseline to week 52]: Number of subjects who gained ≥15 letters from baseline in BCVA, assessed in change from baseline in ETDRS letters over time
• Number of Administrations of Study Drug Required [From baseline to week 52]: The mean number of doses administered during the 52 weeks of study
• Number of Participants With Treatment Emergent Adverse Events [From baseline to week 52]: Number of Participants with Treatment Emergent Adverse Events (Safety and tolerability)
• Number of Subjects With Induced and Boosted Anti-Drug Antibodies [From baseline to week 52]: Number of subjects with induced and boosted Anti-Drug Antibodies (ADA) (Immunogenicity)
• Concentration of Aflibercept in Blood (Pharmacokinetics) [2 Days after Week 16 Injection]: Free Drug Concentration of aflibercept in blood (Pharmacokinetics)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Male or female subjects age ≥ 18 years.
2. Subjects have type 1 or type 2 diabetes mellitus who present with central DME involvement in the study eye.
3. The cause of decreased vision in the study eye has been attributed primarily to DME by the Investigator.
4. Subject is able to understand and voluntarily provide written informed consent to participate in the study.
5. If female of child bearing potential, the subject must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at baseline visit, and should not be nursing or planning a pregnancy.
6. If female, subject must be:

   1. Surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or
   2. Of childbearing potential and practicing an acceptable form of birth control (defined as the use of an intrauterine device; a barrier method, like condom, with spermicide; any form of hormonal contraceptives; or abstinence from sexual intercourse) starting 60 days prior to dosing and continuing at least 90 days following the last treatment.
   3. Of non-childbearing potential (i.e., postmenopausal for at least 1 year).
7. If male, subject must be surgically or biologically sterile. If not sterile, the subject must agree to use an acceptable form of birth control with sexual partner (as described in inclusion criteria #6b of protocol) or abstain from sexual relations during the study period and up to 90 days following the last treatment dose.
8. Subject is willing to comply with the study duration, study visits and study related procedures.

Exclusion Criteria:

1. Subjects with known hypersensitivity to aflibercept or any of the excipients
2. Subjects with current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol
3. Subjects with uncontrolled hypertension defined as systolic blood pressure >160mm Hg or diastolic blood pressure > 95 mm of Hg.
4. Subjects with a history of cerebrovascular accident or myocardial infarction within 6 months of randomization.
5. Subjects with history of use of intraocular corticosteroids anytime in the past or periocular (subconjunctival, intra-scleral, sub-tenon or retrobulbar) corticosteroids within 4 months of randomization
6. Subjects who have only one functional eye, even if the eye met all other study requirements, or who have an ocular condition on the fellow eye with a poorer prognosis than the study eye.

Participant flow

Outcome results

• Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8 (Primary), Least squares mean, BCVA letter score: MYL-1701P 6.60 +/- 0.548; Eylea 6.56 +/- 0.548
• The Mean Change From Baseline in Central Retinal Thickness (CRT) (Secondary), Mean, Micrometer: MYL-1701P -170.14 +/- 7.198; Eylea -167.67 +/- 7.260
• The Mean Change in BCVA (Secondary), Mean, BCVA letter score: MYL-1701P 10.76 +/- 0.619; Eylea 10.52 +/- 0.621
• Number of Subjects Who Gained ≥15 Letters From Baseline in BCVA (Secondary), Count of participants, Participants: MYL-1701P 57; Eylea 51
• Number of Administrations of Study Drug Required (Secondary), Mean, Doses: MYL-1701P 8.4 +/- 2.06; Eylea 8.7 +/- 1.76
• Number of Participants With Treatment Emergent Adverse Events (Secondary), Count of participants, Participants: MYL-1701P 138; Eylea 138
• Number of Subjects With Induced and Boosted Anti-Drug Antibodies (Secondary), Count of participants, Participants: MYL-1701P 5; Eylea 10
• Concentration of Aflibercept in Blood (Pharmacokinetics) (Secondary), Mean, ng/ml: MYL-1701P 34.355 +/- 30.693; Eylea 30.758 +/- 32.3208

Adverse events

Time frame: Baseline to 52 Weeks

Serious adverse events by term

Other adverse events by term

• Results publication: Chauhan R, Gupta V, Natesh S, Vohra R, Agarwal V, Ganapathi PC, Bose D, Loganathan S. Safety and efficacy of biosimilar aflibercept MYL-1701P in diabetic macular oedema: 20-week extension results following the INSIGHT pivotal trial. BMJ Open Ophthalmol. 2026 Jun 29;11(2):e002637. doi: 10.1136/bmjophth-2025-002637. PMID 42373197
• Results publication: Bressler SB, Oleksy P, Alfaro DV, Apte RS, Barve A, Baumane K, Beckmann K, Degi R, Ernest J, Gupta V, Kamei M, Kishino G, Lorenz K, Marcus DM, Bose D, Ganapathi PC, Loganathan S. Comparability of aflibercept biosimilar with reference aflibercept in diabetic macular edema: subgroup analysis of the pivotal Phase-III INSIGHT randomized clinical trial. Expert Opin Biol Ther. 2026 May;26(5):525-534. doi: 10.1080/14712598.2026.2672422. Epub 2026 May 18. PMID 42104207
• Results publication: Bressler SB, Barve A, Ganapathi PC, Beckmann K, Apte RS, Marcus DM, Baumane K, Agarwal S, Oleksy P, Reichstein DA, Patel SS, Ernest J, Degi R, Gupta V, Kishino G, Kamei M, Loganathan S; INSIGHT Study Group. Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema: The INSIGHT Randomized Clinical Trial. JAMA Ophthalmol. 2024 Oct 1;142(10):952-960. doi: 10.1001/jamaophthalmol.2024.3458. PMID 39264599

• Study Protocol (PDF, 2020-06-09)
• Statistical Analysis Plan (PDF, 2021-04-21)