Biosimilar FYB202 Shows Therapeutic Equivalence to Ustekinumab for Plaque Psoriasis

Switching from reference ustekinumab to biosimilar FYB202 maintained comparable efficacy, safety, and immunogenicity in patients with moderate to severe plaque psoriasis. | Image Credit: SNAB - stock.adobe.com

Biosimilar FYB202 or ustekinumab-aauz (Otulfi; Fresenius Kabi) had no clinically relevant effect on efficacy, safety, or immunogenicity and demonstrated therapeutic equivalence to reference ustekinumab in patients with moderate to severe plaque psoriasis, supporting its therapeutic equivalence and potential for broader application in other indications, according to a study published in Advances in Therapy.¹

Even though biological therapies showed improvements in psoriasis management and other inflammatory conditions, high costs continue to limit access. Over the past decade, adalimumab, infliximab, and etanercept biosimilars have been adopted which have helped increase the number of patients who benefit from treatment.

Previous researchers found that patients with psoriasis who received either adalimumab, etanercept, or ustekinumab underwent dose escalations more frequently with ustekinumab compared with the other 2 treatments.² They also discontinued treatment after dose escalation occurred more often with adalimumab and etanercept than with ustekinumab.

Currently, US regulatory bodies require evidence that the molecule is like the reference product in terms of structure, function, pharmacokinetics, clinical efficacy, and safety for biosimilar approval.¹ Researchers have proposed dropping these blanket requirements, deeming them redundant, and modeling regulatory agencies after the United Kingdom and European Union.³

Researchers conducted a multicenter randomized, double blind, parallel group phase 3 study across 27 sites in Estonia, Georgia, Poland, and Ukraine.¹ About 40% of the patient population was women with an average age of 42 years, with a 24.4 mean Psoriasis Area and Severity Index (PASI) score. Of the patients, 19.4% reported prior systemic biological treatment for psoriasis, and only 9.2% of these reported an inadequate response or intolerance.

Researchers randomized a total of 392 patients to either FYB202 (n = 197) or reference ustekinumab (n = 195). Some patients did not respond (FYB202, 4; reference ustekinumab, 5), and a few patients in the reference ustekinumab group did not undergo rerandomization due to adverse events (AEs) leading to study discontinuation (n = 2) or nonattendance at week 28 (n = 1).

In the FYB202 group, 189 patients continued treatment to week 52, and researchers rerandomized 186 in the reference group (FYB202, 89; reference ustekinumab, 97). Following rerandomization, 372 patients completed the study until week 52. There were 187 patients who remained on FYB202, 97 patients who remained on reference ustekinumab, and 88 patients who switched from reference ustekinumab to FYB202.

Patients treated with FYB202 showed an estimated mean percent improvement in PASI score of 79.5% (95% CI, 74.6%-84.4%) for the primary end point from baseline to week 12, while patients treated with reference ustekinumab achieved 76.2% (95% CI, 71.5%-81%). All secondary efficacy end points were also similar between treatment groups.

Percentages of patients who reached PASI 75 (FYB202, 97.9%; reference ustekinumab, 96.4%) and PASI 90 (FYB202, 81.7%; reference ustekinumab, 78.2%) at week 28 were similar. Switching from reference ustekinumab to FYB202 had no impact on therapeutic efficacy. A total of 97.7% patients in the switch group maintained their PASI 75 response at week 52.

No differences emerged between the groups that maintained their initial treatment for the entire 52 weeks. A PASI 75 response at week 52 was maintained by 96.2% of patients in the FYB202 group and 94.6% of patients in the reference ustekinumab group.

Both treatments patients tolerated well, and researchers found the safety profiles comparable between groups. Patients reported at least 1 AE during the first 28 weeks in 39.6% of the FYB202 group and 41% of the reference group. Before rerandomization, patients most frequently reported injection site pain (FYB202, 11.2%; reference ustekinumab 7.7%), nasopharyngitis (FYB202, 4.6%; reference ustekinumab, 2.6%), and COVID-19 (FYB202, 3.6%; reference ustekinumab, 2.6%).

AEs caused 1% of patients treated with FYB202 and 1.5% of patients treated with reference ustekinumab to withdraw from the study. After rerandomization, 3 patients in the FYB202 group, 1 patient in the reference ustekinumab group, and 1 patient in the reference ustekinumab to FYB202 switch group reported serious AEs. Only 1 patient in the reference ustekinumab to FYB202 switch group discontinued because of an AE (congenital anomaly).

At baseline, 5.1% of patients in the FYB202 group and none in the reference ustekinumab group had confirmed positive adenosine deaminase (ADA) tests. ADA prevalence from week 4 to week 52 was lower for FYB202 compared with reference ustekinumab. Researchers observed the maximum proportion of patients with ADAs at week 28 in both groups.

After rerandomization, ADA and neutralizing antibody positivity declined in all 3 groups. No patients who were ADA negative at week 28 became ADA positive following the switch from reference ustekinumab to FYB202, indicating that the switch from reference ustekinumab to FYB202 did not impact immunogenicity. Mean percent improvement in PASI score from baseline to week 12 was slightly lower in ADA positive patients compared with ADA negative patients, and both treatment groups showed a similar reduction.

Researchers observed higher geometric mean C_trough levels for patients treated with FYB202 compared with patients treated with reference ustekinumab, especially at early time points, which may be due to the differences in ADA incidences at the early time points as well some differences in the protein content. The serum C_trough levels of ustekinumab showed a high interpatient variability particularly at weeks 4 and 12. Researchers observed smaller interpatient variability during steady state at weeks 16, 28, 40, and 52. They also observed similar and stable C_trough levels from week 16 to week 52 in all 3 rerandomized groups from week 28 to week 52.

The study was not powered for statistical comparisons of equivalence after switching from reference ustekinumab to FYB202. Researchers included only a single switch, but clinical practice may involve multiple treatment switches. Additionally, regulatory authorities required the trial to detect differences between treatments for biosimilar approval, not to prove de novo efficacy. Researchers selected a narrower patient population than clinical practice might expect to ensure comparison sensitivity. Finally, the study lacked racial diversity as all patients were White, but extrapolation allows inferring similar treatment effects for other populations.

“Using a totality of evidence approach, proof of therapeutic equivalence in this sensitive psoriasis population allows for extrapolation to other indications, with similar clinical performance of FYB202 and reference ustekinumab assumed across all approved indications,” study authors concluded.

References

1. Papp K, Balser S, Nopora K, et al. A randomised, double-blind trial to compare the efficacy, safety, and immunogenicity of the biosimilar ustekinumab FYB202 with reference ustekinumab in patients with moderate-to-severe plaque psoriasis. Adv Ther. 2025;42:2135-2149. doi:10.1007/s12325-025-03138-2

2. Santoro C. Differences in psoriasis treatment: ustekinumab dose escalation vs adalimumab, etanercept discontinuation. The Center for Biosimilars^®. May 22, 2025. Accessed June 9, 2025. https://www.centerforbiosimilars.com/view/differences-in-psoriasis-treatment-ustekinumab-dose-escalation-vs-adalimumab-etanercept-discontinuation

3. Niazi SK. BioRationality: a new bill to transform the future of biosimilars. The Center for Biosimilars. May 5, 2025. Accessed June 9, 2025. https://www.centerforbiosimilars.com/view/biorationality-a-new-bill-to-transform-the-future-of-biosimilars