Pavblu, a biosimilar to Eylea, also showed no clinically meaningful differences in efficacy, safety, and immunogenicity in patients with neovascular age-related macular degeneration (nAMD).
Aflibercept-ayyh (ABP 938, Pavblu; Amgen), a biosimilar of aflibercept (Eylea; Regeneron Pharmaceuticals), demonstrated no clinically meaningful differences in efficacy, safety, and immunogenicity compared with its reference product when treating patients with neovascular (wet) age-related macular degeneration (nAMD). Importantly, these findings were maintained even when patients receiving reference aflibercept transitioned to the biosimilar at the 16-week point.1
Trial Name: A Study to Understand Effectiveness and Safety of ABP 938 Compared to Aflibercept (Eylea®) in Patients Suffering With Neovascular Age-related Macular Degeneration [Neovascular (Wet) AMD]
ClinicalTrials.gov ID: NCT04270747
Sponsor: Amgen
Completion Date: January 30, 2023
Pavblu is the fifth biosimilar of Eylea to be approved by the FDA. At the time of its approval in 2024, it was approved with a skinny label that included nAMD, macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy indications.2 It demonstrated its structural and functional similarity to its reference product in a study published in Ophthalmology and Therapy; specifically, it showed that it had the same amino acid sequence and exhibited both secondary and tertiary structures as well as biological activity as Eylea. There were only minor differences in a small number of biochemical attributes, but these were not anticipated to impact the biosimilar’s clinical performance, wrote the investigators.3
The current data1 are from a randomized, double-masked, active-controlled, multiregional clinical trial (NCT04270747),4 which enrolled 579 patients with active treatment-naive choroidal neovascularization secondary to nAMD from 102 health centers across 16 countries. Evaluable patients (N = 576) were randomly assigned to receive either 2 mg of Pavblu (n = 288) or Eylea (n = 288) via intravitreal injection every 4 weeks for the first 3 doses, then every 8 weeks through week 48. At week 16, patients in the Pavblu group continued to receive treatment with the biosimilar, whereas those receiving Eylea were randomly assigned again to continue receiving the reference product (n = 136) or transition to its biosimilar (n = 134).1,4
The primary efficacy end point was the least squares mean difference in change in best-corrected visual acuity (BCVA), measured by Early Treatment Diabetic Retinopathy Study letter score, from baseline to week 8. Secondary efficacy end points were safety and immunogenicity, which were analyzed descriptively. In a substudy of patients, serum drug concentration profiles were also assessed.1,4
The findings demonstrated that demographic and baseline characteristics and exposure to treatment were similar between the treatment groups. Among initially randomly assigned patients, the least squares mean difference in change from baseline in BCVA at week 8 between Pavblu and Eylea was about 0.1 (95% CI, –1.3 to 1.5; and 90% CI, –1.1 to 1.3), falling within prespecified similarity margins (–3.9, 3.9, and –3.3, respectively). With this result, the primary clinical efficacy end point was met, wrote the study authors. Additionally, secondary efficacy end points (parallel-arm and post transition) were overall similar between groups. A low and similar incidence of binding antidrug antibodies was observed in all groups, and the substudy confirmed low systemic exposure of free drug concentrations of the biosimilar and its reference product.1
At the patient level, through the parallel-arm period, adverse events (AEs) were reported in approximately 39.2% (n = 113) and 37.2% (n = 107) of patients in the Pavblu and Eylea groups, respectively. Most AEs were grade 1 or 2 in severity, according to the Common Terminology Criteria for Adverse Events. For both treatment groups, the most frequently reported AE was conjunctival hemorrhage, which occurred in 4.2% (n = 12) of those receiving the biosimilar and 3.8% (n = 11) receiving the reference product. Other AEs observed in either treatment group were nAMD, hypertension, and COVID-19, and there were no notable differences in frequency of AEs by preferred term by treatment groups.
Further, in the posttransition period, AEs were reported in 52.7% (n = 144) of those who continued to receive Pavblu, 52.9% (n = 72) of those who continued to receive Eylea, and 57.1% (n = 76) of those who transitioned from the reference product to its biosimilar. The most frequently reported AE in the 3 treatment groups was nAMD, which was reported in 5.9% (n = 16), 8.1% (n = 11), and 7.5% (n = 10) of patients in these respective groups.1
“This 52-week randomized, double-masked, active-controlled, comparative clinical study demonstrated comparative similarity in efficacy of [Pavblu] and [Eylea] in participants with nAMD. The overall safety and immunogenicity were also similar between [the 2 treatments] over the entire study period. In addition, this study demonstrated that the efficacy, safety, and immunogenicity were not altered by a transition from [the reference] to [its biosimilar],” concluded the study authors. “These clinical results, along with previously published data demonstrating similarity of [Pavblu] to [Eylea] in analytical and functional characteristics and nonclinical analysis contribute to the [totality of evidence] demonstrating similarity of [Pavblu] with [Eylea].”1
