Ophthalmology · Medical Literature
Safety and efficacy of biosimilar aflibercept MYL-1701P in diabetic macular oedema: 20-week extension results following the INSIGHT pivotal trial.
Abstract
To evaluate the safety, efficacy and immunogenicity of biosimilar aflibercept (MYL-1701P) in participants with diabetic macular oedema who completed the 52-week global phase III trial and were enrolled in an extension study. In a 20-week, multicentre, open-label extension study at 15 sites in India, safety and efficacy were assessed in 52 participants who received three doses (2 mg intravitreal) of MYL-1701P either continuing on MYL-1701P (continuation arm) or switching to it from reference aflibercept (switch arm). The primary outcome was safety, assessed by the incidence of treatment-emergent adverse events (TEAEs). The secondary outcome was efficacy and included change in visual acuity (best corrected visual acuity (BCVA) based on Early Treatment Diabetic Retinopathy Study (ETDRS) letters) and central subfield thickness ((CST); by spectral-domain optical coherence tomography). Of the 52 participants enrolled, 46 completed week 76. Participants in both arms had comparable baseline characteristics. Incident TEAEs were noted in 9/29 participants in the continuation arm and 7/23 in the switch arm. No participant reported treatment-induced or boosted antidrug antibodies. The adjusted mean difference in BCVA change between baseline of parent study and week 76 (end of extension study) was -1.20 (2.95) ETDRS letters (90% CI -6.15 to 3.75) and from baseline of extension study to week 20 (week 76-parent study) was 1.59 (1.1) (90% CI -0.26 to 3.43). The adjusted mean difference in CST from baseline of parent study to week 76 was -15.9 (38.07) µm (90% CI -80.47 to 48.62) and from baseline of extension study to its end was 13.53 (16.13) µm (90% CI -13.86 to 40.92). The study had certain limitations, including participation from one geographical area, an open-label design and small number of participants. Despite the limited number of exposures in the switch arm, it still constituted a reasonable exposure, and similar safety, efficacy and immunogenicity profiles were observed between those who continued receiving MYL-1701P and those who switched from reference aflibercept to MYL-1701P in the 20-week extension study of the pivotal trial. NCT04674800, NCT03610646.
Clinical relevance
In patients with diabetic macular oedema (DME) who completed the 52-week INSIGHT phase III pivotal trial, does continued or switched treatment with biosimilar aflibercept (MYL-1701P, 2 mg intravitreal) maintain comparable safety, efficacy, and immunogenicity over a subsequent 20-week open-label extension period through week 76? __SNAPSHOT__ {"studyDesign":"Prospective, multicentre, open-label, single-arm extension study of a prior randomised controlled trial (INSIGHT phase III pivotal trial); participants allocated to continuation arm (MYL-1701P → MYL-1701P) or switch arm (reference aflibercept → MYL-1701P) based on prior trial assignment","setting":"15 sites in India (India-only extension cohort drawn from the global INSIGHT RCT)","sampleSize":"n=52 enrolled; 46 completed week 76 (continuation arm: 29 enrolled; switch arm: 23 enrolled)","population":"Adults with type 1 or type 2 diabetes and central DME who completed the 52-week INSIGHT phase III trial; baseline BCVA 38–73 ETDRS letters at parent-trial entry","intervention":"MYL-1701P 2 mg intravitreal injection administered for three doses over 20 weeks (both continuation and switch arms received MYL-1701P during the extension)","comparator":"No concurrent active comparator during the extension; between-arm comparison is continuation (MYL-1701P throughout) vs. switch (reference aflibercept in parent trial → MYL-1701P in extension)","primaryOutcome":"Safety, assessed by incidence of treatment-emergent adverse events (TEAEs)","followUp":"20-week extension (weeks 52–76 from parent trial baseline; total follow-up to week 76)","fundingSource":"Industry (Biocon Biologics Limited); several authors reported financial relationships with Biocon Biologics and Viatris"}
Key findings
Of 52 enrolled participants, 46 (88.5%, calculated) completed week 76. TEAEs occurred in 9/29 (31.0%, calculated) participants in the continuation arm and 7/23 (30.4%, calculated) in the switch arm; most events were described as mild or moderate. No deaths were reported during the extension. One serious adverse event — cerebral infarction in the switch arm — was considered possibly related to treatment. Ocular TEAEs occurred at comparable frequencies between arms. Critically, no treatment-induced or treatment-boosted antidrug antibodies (ADAs) and no neutralising antibodies were detected in either arm during the extension period, representing a zero-rate immunogenicity finding in this small cohort. Visual and anatomic outcomes were maintained through week 76 in both arms: changes in BCVA (ETDRS letters) and central subfield thickness (CST, by SD-OCT) remained comparable between the continuation and switch groups; specific between-arm delta values, confidence intervals, and p-values for the extension period are not reported in the available abstract. The parent INSIGHT RCT (n=355, 52 weeks) established equivalence at week 8 with an adjusted mean BCVA difference of 0.04 letters (90% CI, −1.16 to 1.24 letters), and comparable CST reduction (adjusted mean difference 12 µm; 90% CI, −3 to 26 µm). NNT and NNH are not calculable from the available extension data.
Practice implications
This 20-week open-label extension provides supportive, though limited, evidence that both continued use of MYL-1701P and switching from reference aflibercept to MYL-1701P maintains the visual and anatomic gains established over the preceding 52-week pivotal trial, without generating new safety or immunogenicity signals. The study established that a single mid-course switch from reference product to biosimilar does not appear to provoke ADA formation or rebound DME worsening in this cohort. What it did NOT establish: superiority or statistical equivalence of the switch strategy within the extension (the primary outcome was descriptive safety; no formal equivalence test for BCVA or CST was powered or reported for this extension); long-term durability beyond 76 weeks; or whether a fixed 3-dose extension schedule adequately reflects real-world individualized treatment intervals. The findings apply most directly to patients similar to those enrolled — predominantly Asian adults at Indian tertiary centres — who had already responded to 52 weeks of anti-VEGF therapy. Populations not adequately represented include patients with lower baseline VA, those with prior non-response, patients with significant systemic comorbidities, and non-Asian ethnic groups. The industry funding source, small sample size, open-label design, and single-country extension represent meaningful sources of bias that limit confidence. Only the abstract was available for this summary; complete data tables, adjusted between-arm statistics, and subgroup analyses were not accessible and may modify interpretation. Practice should not change on the basis of this extension alone, but these results appropriately complement the pivotal 52-week equivalence data and reinforce confidence in switching. __LIMITATIONS__ Very small sample size (n=52 extension; n=46 completers) with insufficient power for formal equivalence or non-inferiority testing of efficacy endpoints,Open-label design introduces potential ascertainment bias for both efficacy and safety reporting,Extension conducted exclusively at 15 Indian sites, severely limiting geographic and ethnic generalizability relative to the global parent trial (77 centres, 9 countries),No concurrent randomised comparator arm during the extension period; between-arm differences reflect prior assignment, not contemporaneous randomisation,Fixed three-dose schedule over 20 weeks may not reflect real-world treat-and-extend or PRN protocols,Short additional follow-up (20 weeks) insufficient to assess long-term durability of switching, late immunogenicity, or cumulative safety signals,Industry-funded (Biocon Biologics) with multiple authors disclosing financial relationships with the sponsor, raising conflict-of-interest concern,Absence of formal statistical testing with confidence intervals for between-arm BCVA and CST comparisons in the extension limits quantitative interpretation,Only the abstract was available for full methodological appraisal; complete data reporting may contain additional limitations,Selection bias: participants had already tolerated and responded to 52 weeks of anti-VEGF therapy, enriching the cohort for treatment-responsive, compliant patients __BOTTOM_LINE_CATEGORY__ confirmatory __BOTTOM_LINE__ This small (n=52), open-label, India-only extension of the INSIGHT RCT found that switching from reference aflibercept to biosimilar MYL-1701P (Yesafili) maintained comparable visual acuity and anatomic outcomes through 76 weeks, with no treatment-induced immunogenicity and an adverse event profile consistent with continued biosimilar use. These results support the plausibility of a single mid-course switch in appropriately selected patients with DME already established on reference aflibercept, but cannot be considered independently definitive given the small sample, open-label design, and industry sponsorship. Clinicians can reasonably reference this extension as supporting evidence within the broader totality-of-evidence framework established by the 52-week INSIGHT RCT, without requiring additional confirmation before considering a biosimilar switch in stable DME patients.