SEATTLE — In two registration trials, aflibercept biosimilars produced results much like those of the reference drug in participants with two forms of macular disease. These biosimilar agents may reduce the cost of intravitreal injections and enable more patients to receive effective intervention early to forestall or prevent blindness.
The phase 3 trials are the 56-week trial of SB15 (Samsung Bioepis) in participants with neovascular age-related macular degeneration (nAMD) and the 24-week trial of CT-P42 (Celltrion) in participants with diabetic macular edema (DME). The data were presented at the 2023 annual meeting of the American Society of Retina Specialists.
SB-15 in nAMD
In the double-masked, multicenter nAMD trial, 449 participants were randomly assigned to receive 2 mg of either SB15 or reference aflibercept — marketed as Eylea by Regeneron Pharmaceuticals — every 4 weeks for three consecutive treatments, then treatment every 8 weeks until week 48. At week 32, participants were re-randomized to continue receiving SB15 (n = 219), continue receiving reference aflibercept (n = 108), or switch treatment from reference aflibercept to SB15 (n = 111). By study end, 425 participants (97%) had completed all 56 weeks of the study.
The primary endpoint of the trial was change from baseline in best corrected visual acuity (BCVA) at week 8. By week 48, improvement in this measure was comparable between the groups, according to the researchers. Mean change in letters from baseline was 7.3 for the SB15 group, 7.5 for the reference aflibercept group, and 7.9 for the group who switched treatment. No new anti-drug antibodies were noted to have developed in the participants whose treatment was switched from reference aflibercept to SB15.
"Growing information indicates that switching from reference products to biosimilars is safe and effective," said Min Sagong, MD, PhD, a professor at Yeungnam University College of Medicine, in Daegu, South Korea, who presented the findings at the meeting and published them in June in JAMA Ophthalmology.
The biosimilar appeared to be as effective as the reference drug for outcomes including BCVA, central subfield thickness, and fluid status up to week 56, Sagong said. "Safety data were comparable without intraocular inflammation, retinal vasculitis, or vascular occlusion. Also, immunogenicity and PK profiles supported the similarity between the two drugs," he said.
CT-P42 in DME
The double-masked, active-controlled trial of CT-P42 included 360 participants with a central subfield thickness of at least 350 micrometers and a BCVA score of 73 to 34 letters in the study eye. Participants were randomly assigned to receive 2 mg of CT‑P42 (n = 180) or reference aflibercept (n = 180) by intravitreal injection every 8 weeks after four initial monthly injections. More than 95% of those in each group completed the study.
The study's primary endpoint, mean change in BCVA from baseline at week 8, was met, according to David Brown, MD, director of clinical research at Retina Consultants of Texas in Houston, who led the trial.
Brown said the week 8 timepoint is typically used in registration studies of biosimilar intravitreal agents because vision improves most in the early study period and any difference in efficacy would become apparent within 2 months.
"Regulatory agencies feel that the sharp part of the curve where the visual acuity is going up is the most sensitive place to detect if your biosimilars weren't as effective as the reference product," he said.
Change in BCVA was similar for both agents. By week 8, the group who received CT‑P42 had gained 9.4 letters, compared with 8.9 letters in the group who received reference aflibercept. "You see that this favors CT-P42 a little bit, but there's really no significant difference," Brown said.
Secondary endpoints assessed at week 52 included efficacy in terms of the proportion of 15-letter gainers, mean change from baseline in central subfield thickness, and proportion of participants with at least a two-step improvement from baseline in Diabetic Retinopathy Severity Score.
The safety profile of the biosimilar agent was also similar to that of reference aflibercept, Brown said. The percentage of participants who experienced treatment-emergent adverse events (TEAEs) was 50.3% for CT-P42 and 53.7% for reference aflibercept. The proportion of participants who had at least one thromboembolic TEAE was the same for both groups, at 1.7%. No differences in injection-related TEAEs were observed between groups.
"These results show that [CT-P42] aflibercept is aflibercept. It walks like a duck, it quacks like a duck, it's a duck," Brown said. "It's performing like we expect aflibercept to perform in a diabetic eye."
Celltrion reportedly filed for US regulatory approval in June.
The SB15 study was funded by Samsung Bioepis. The CT-P42 study was funded by Celltrion. Sagong reports consultancies for and contracts with Alcon, Allergan/AbbVie, Alteogen, Bayer, Celltrion, Curacle, Novartis, Roche, and Samsung. He is a member of the Speaker Bureaus for Allergan/AbbVie, Bayer, Novartis, and Roche. Brown reports consultancies for Genentech/Roche and Regeneron/Bayer and is a consultant to the Regeneron Combination Products Steering Committee
2023 Annual Meeting of the American Society of Retina Specialists. Presented July 29-30, 2023.
A former staff reporter for Cardio magazine and contributor to MD Magazine's vision disease coverage, Ellen Kurek earned her nonfiction writing certificate from the University of Washington.
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