The study met its primary endpoint of PASI improvement in the biosimilar and bio-originator cohorts.
The ustekinumab biosimilar, AVT04 demonstrated therapeutic equivalence to the reference product, including comparable safety and tolerability, in patients with moderate-to-severe chronic psoriasis (PsO), according to Expert Opinion on Biological Therapy.1
“The development of biosimilars is a difficult process due to the complex molecular structure of the reference biologics,” wrote Steven R Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, and colleagues. “Various regulations and guidelines have been put in place for the development and licensing of biosimilar products. Currently, no biosimilar to the reference product has been approved.”
Ustekinumab, an interleukin-12 (IL-12) and IL-23 inhibitor, is approved to treat a variety of inflammatory diseases, including PsO. AVT04 is a potential biosimilar option being developed for both subcutaneous and intravenous use.2
The multicenter, double-blind, 52-week study evaluated safety, efficacy, tolerability, immunogenicity, and pharmacokinetics (PK) between AVT04 and originator ustekinumab in this patient population. Participants were randomized 1:2 to receive the biosimilar or bio-originator, respectively. Eligible patients were adults with moderate-to-severe PsO for ≥6 months and included involved body surface area (BSA) ≥10%, static Physician’s Global Assessment (sPGA) ≥3, and PASI ≥12 at screening and baseline, among others.
The study was divided into 2 stages: the primary efficacy assessment (week 1 to week 15) and the long-term safety and efficacy assessment (week 16 to week 52). Patients received treatment at weeks 1, 4, 16, 28, and 40. At the 16-week mark, patients with ≥50% improvement in the psoriasis area and severity index (PASI) in the biosimilar cohort remained on AVT04 treatment, while patients in the ustekinumab cohort were randomized to switch to the biosimilar or continue receiving the reference product.
The primary endpoint was the improvement in PASI between baseline and week 12. Other endpoints included changes in BSA and the proportion of patients achieving sPGA responses of clear or almost clear. Equivalence was determined if the confidence interval (CI) for the adjusted difference in means was within the ±10% equivalence margins (90% CI).
A total of 581 patients were included, 544 of which completed the study, with 194 placed in the AVT04 group and 387 in the reference product group. Most (62.7%) patients were male, 94.3% were aged <65 years, and 99.3% were non-Hispanic/Latino.
The study met its primary endpoint, with 87.3% PASI improvement in the biosimilar cohort and 86.8% PASI improvement in the bio-originator cohort (CI: -2.14%, 3.01%). Additionally, the proportion of patients achieving PASI50, PASI75, PASI90, and PASI100 prior to and after switching was similar across treatment arms and no clinically significant differences were observed between groups throughout the study.
The safety, efficacy, and PK profiles were similar across treatment groups. The incidence of antibodies to ustekinumab did not demonstrate clinically meaningful impact. At week 16, 67 patients (34.5%) experienced 104 treatment-emergent adverse events (TEAEs) in the biosimilar cohort compared with 130 patients (33.6%) in the reference product cohort. Most TEAEs were mild, with the majority categorized as unrelated to treatment assignment.
“The findings add to the totality of evidence supporting biosimilarity, which in turn reinforces the assertion that the risks and benefits for patients receiving AVT04 will be the same for this patient population as those established for the reference product,” investigators concluded. “The evidence also supports the scientific rationale for potential extrapolation to other approved indications of ustekinumab.”