The Totality of Evidence of Ustekinumab Biosimilar SB17

A review article outlined the totality of evidence supporting efficacy and safety of SB17, a ustekinumab biosimilar.

SB17, a new ustekinumab biosimilar, demonstrates comparable efficacy and safety for psoriasis and psoriatic arthritis, enhancing patient experience and convenience. | Image credit: Oporty786 - stock.adobe.com

SB17 is a monoclonal antibody targeting the p40 subunit of interleukins (ILs) 12 and 23, cytokines involved in the inflammatory process common to several immune-mediated inflammatory diseases. The originator (Stelara) was approved by the FDA and European Medicines Agency (EMA) in 2009 to treat moderate to severe plaque psoriasis. It was later approved for other indications, including psoriatic arthritis, Crohn disease, and ulcerative colitis.

SB17, 1 of 7 Stelara biosimilar competitors, was approved in 2024 by the FDA and EMA, based on the totality of evidence demonstrating biosimilarity. First, analytical studies established similarity to the reference product sourced from both the US and Euroepan Union in structural and physicochemical characteristics and biological activity. A phase 1 study in healthy volunteers confirmed similar pharmacokinetic parameters between SB17 and the reference product.

Finally, a phase 3 randomized, double-blind trial in 503 patients with moderate to severe plaque psoriasis across 45 centers in 8 countries showed that SB17 had similar efficacy to the reference product at 28 weeks, with an 85% reduction from baseline in psoriasis area severity index (PASI) observed in both groups, and comparable safety profiles. Patients were re-randomized at 28 weeks to continue SB17, continue the reference ustekinumab, or switch from the reference product to SB17. At week 52, the percent change in PASI from baseline, as well as treatment-emergent adverse events, were comparable between the 3 groups.

Notably, SB17 has shown a lower immunogenicity profile compared to the ustekinumab originator. The authors noted that neutralizing antidrug antibodies “can pose serious clinical consequences,” since they can reduce the effectiveness of the molecule. Five ustekinumab biosimilars including SB17 have shown lower immunogenicity compared to the reference product. In the SB17 phase 3 clinical trial for example, the antidrug antibodies positivity rates for the biosimilar and originator were 13% and 39% up to week 28, and 14% and 35% of patients were positive for neutralizing antibodies. However, although lower immunogenicity was observed, there were no differences in clinical outcomes between the reference ustekinumab and biosimilar SB17, suggesting that antidrug antibodies do not impair the clinical efficacy of the originator in patients with psoriasis, the reviewers added.

As dysregulation of IL-12 and IL-23 signaling in Th1/Th17 cells “is central to the development of chronic inflammation and pathology” associated with immune-mediated inflammatory diseases, the mechanism of action of SB17, binding the p40 subunit of IL-12 and IL-23, provided the basis for extrapolation from psoriasis to additional immune-mediated inflammatory diseases including psoriatic arthritis, Crohn disease, and ulcerative colitis

Additional features of SB17 may “contribute to an improved patient experience” over the reference product, the reviewers said. Both the reference product and SB17 have been approved for administration via intravenous infusion or a prefilled syringe for subcutaneous injections. The authors noted that the SB17 prefilled syringe “has been designed to streamline the drug administration process for patient and health care professionals,” with improvements over the originator pre-filled syringe. The SB17 prefilled syringe is latex-free and uses a thinner needle size than the originator, which could improve patients’ comfort and their adherence to treatment. The SB17 pre-filled syringe also includes a needle safety guard to prevent needle stick injuries.

Furthermore, SB17 can be stored more conveniently than the reference product.Once the reference product has been removed from refrigeration and stored at room temperature, it cannot be refrigerated again. The SB17 prefilled syringe can be returned to refrigeration once within 1 month of being stored at room temperature, offering more flexibility and likely reducing waste.

Several factors may hinder the uptake of ustekinumab biosimilars, including health care professionals’ concerns. The complexity of the biologic manufacturing process, with inherent variability, can lead to differences not only between originator biologics and biosimilars, but between different batches of the same biologic. According to the reviewers, understanding that variations exist between different batches of the reference product could help alleviate the concerns of patients and health care professionals about the effectiveness and safety of biosimilars. Publication of additional real-world evidence in extrapolated indications can also help to build confidence in ustekinumab biosimilars.

Reference

Cheon JH, Duk Ye B, Armuzzi A, Rieder F, Girolomoni G, Puig L, Jung H, Feldman SR. The 'totality of evidence' and 'extrapolation' of SB17, a ustekinumab biosimilar. Expert Opin Biol Ther. 2025;25(6):615-632. doi:10.1080/14712598.2025.2508838