Aflibercept Biosimilar Demonstrates Therapeutic Equivalence for DME

CT-P42, an investigational aflibercept biosimilar, has demonstrated therapeutic equivalence in people with diabetic macular edema (DME) in new phase 3 data.1

"In high-income countries with abundant resources, where patients can benefit from intensive therapy, intravitreal anti-VEGF therapy is currently widely used to treat DME. However, in low- or intermediate-resource settings, where the prevalence of DME may be higher, this option may not be possible, requiring less expensive alternatives to be considered,” lead investigator Sebastian Wolf MD, PhD, Department of Ophthalmology, Inselspital, Bern University Hospital, Bern, Switzerland, and colleagues wrote.1

In the active comparator trial, Wolf and colleagues randomized 348 participants, 173 to CT-P42 and 175 to reference aflibercept, to receive 2 mg/0.05 ml) by intravitreal injection every 4 weeks (5 doses), then every 8 weeks (4 doses), in the main study period. Participants had a diagnosis of either type 1 or 2 diabetes mellitus with DME involving the center of the macula.1

The investigators found that best-corrected visual acuity (BCVA) improved from baseline to week 8 in both groups, with a least squaresmean improvement of 9.43 (standard error [SE], 0.798) and 8.85 (SE, 0.775) letters in the CT-P42 and reference aflibercept groups, respectively, for an estimated between-group treatment difference of 0.58 letters, with the CIs within the predefined equivalence margin of ±3 letters (95% CI, −0.73 to 1.88 [global]; 90% CI, −0.52 to 1.67 [FDA]).1

Additionally, through week 24, there were similar improvements between participants treated with CT-P42 and reference aflibercept in change in BCVA and retinal central subfield thickness, and ETDRS Diabetic Retinopathy Severity Scale score. Pharmacokinetics, usability, and immunogenicity were comparable between groups, and in terms of safety, there were similar proportions of patients that experienced at least 1 treatment-emergent adverse event (CT-P42, 50.3%; reference aflibercept,53.7%). Further data through week 52 will be announced in the future.1

“The results of this study support the potential of CT-P42 as a candidate biosimilar for reference aflibercept: an effective therapy for DME, for which high costs can limit patient access and potentially contribute to treatment discontinuation. The availability of an aflibercept biosimilar may help to overcome these issues, and ultimately improve the global management of DME,” Wolf and colleagues wrote.1

Other recent research on aflibercept in DME, from a subgroup analysis of the Phase 2/3 PHOTON trial, revealed visual and anatomical improvements with aflibercept 8 mg treatment trended numerically higher in patients with DME without a history of prior treatment.2

The research showed non-inferior BCVA gains with aflibercept 8 mg with extended dosing intervals, compared with aflibercept 2 mg, in patients with DME, without new safety signals through Week 96. As approximately 44% of these patients had received prior treatment for DME, Garg and colleagues highlighted the opportunity to assess treatment outcomes by treatment history.2

“Our new treatments work really well, and they work well with less frequent dosing over time. That's a big deal for all of our patients, particularly for our diabetic patients, who tend to be younger working-age adults,” Garg told HCPLive. “Although it works well for both previously treated eyes as well as treatment-naive eyes, if you have patients who had previous treatment, they may benefit from slightly more frequent 8 mg dosing.”

REFERENCES

1. Wolf S, Stanga PE, Veselovsky M, et al. Biosimilar Candidate CT-P42 in Diabetic Macular Edema: 24-Week Results from a Randomized, Active-Controlled, Phase III Study. Ophthalmol. Retina. 2024:8 (12): p. 1163-1173

2. Garg SJ. Outcomes with Aflibercept 8 mg and 2 mg by Prior DME Treatment Status: A Subgroup Analysis of the Phase 2/3 PHOTON Trial. Poster presented at the American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.