In the realm of immunotherapy, the emergence of SB17, a groundbreaking ustekinumab biosimilar, has orchestrated a harmonious blend of efficacy and safety for patients grappling with psoriasis and psoriatic arthritis, resonating with the melody of enhanced patient experience and convenience.
An enlightening review article has meticulously delineated the symphony of evidence that fortifies the foundation of SB17, a remarkable biosimilar of ustekinumab. This monoclonal antibody takes aim at the p40 subunit of interleukins (ILs) 12 and 23, pivotal cytokines entangled in the inflammatory cascade that underpins various immune-mediated inflammatory diseases. The progenitor of this biosimilar, Stelara, received the FDA and EMA’s nod back in 2009 for treating moderate to severe plaque psoriasis before expanding its spectrum to encompass psoriatic arthritis, Crohn’s disease, and ulcerative colitis.
SB17, standing tall among 7 Stelara biosimilar contenders, clinched the approval seal of both the FDA and EMA in 2024, grounded on a bedrock of evidence showcasing its biosimilarity. The journey commenced with analytical studies that meticulously unveiled the structural, physicochemical, and biological resemblance between SB17 and the reference product sourced from both the US and the European Union. A phase 1 study in healthy volunteers further cemented this kinship by affirming the similarity in pharmacokinetic parameters between SB17 and its reference counterpart.
The crescendo of evidence reached its peak with a phase 3 randomized, double-blind trial that unfolded in 503 patients grappling with moderate to severe plaque psoriasis across 45 centers in 8 countries. SB17 strutted its prowess by demonstrating comparable efficacy to the reference product at the 28-week mark, with both groups exhibiting an 85% reduction from baseline in psoriasis area severity index (PASI), alongside akin safety profiles. Following this, patients underwent a re-randomization at week 28 to either persist with SB17, continue the reference ustekinumab, or transition from the reference product to SB17. By week 52, the percent change in PASI from baseline, along with treatment-emergent adverse events, danced in synchrony across the three groups.
A striking revelation surfaced as SB17 unfurled a lower immunogenicity profile compared to the ustekinumab progenitor. The presence of neutralizing antidrug antibodies, capable of orchestrating grave clinical ramifications by diminishing the molecule’s efficacy, was notably subdued in SB17. This revelation was echoed in the SB17 phase 3 clinical trial, where the rates of antidrug antibodies positivity for the biosimilar and originator stood at 13% versus 39% until week 28, with 14% versus 35% of patients testing positive for neutralizing antibodies. Despite this disparity, clinical outcomes between the reference ustekinumab and biosimilar SB17 remained unscathed, suggesting that antidrug antibodies failed to impede the clinical efficacy of the originator in psoriasis patients.
Delving into the philosophical underpinnings, the dysregulation of IL-12 and IL-23 signaling in Th1/Th17 cells emerges as the epicenter fueling the genesis of chronic inflammation and pathology intertwined with immune-mediated inflammatory diseases. SB17’s mechanism of action, entailing the binding of the p40 subunit of IL-12 and IL-23, not only elucidates its efficacy in psoriasis but also lays the groundwork for extrapolation to a myriad of immune-mediated inflammatory diseases, including psoriatic arthritis, Crohn’s disease, and ulcerative colitis.
In the realm of patient experience, SB17 emerges as a beacon of innovation, promising an enhanced journey compared to the reference product. Both the biosimilar and the reference ustekinumab have garnered approval for administration through intravenous infusion or a prefilled syringe for subcutaneous injections. Noteworthy enhancements in the SB17 prefilled syringe, designed to streamline the drug administration process for patients and healthcare professionals, stand out. This latex-free marvel boasts a thinner needle size compared to its originator, promising heightened comfort for patients and bolstering adherence to treatment. Furthermore, the inclusion of a needle safety guard in the SB17 prefilled syringe serves as a shield against needle stick injuries, encapsulating a narrative of patient-centric care.
Additionally, the convenience quotient tilts in favor of SB17, as it offers a more flexible storage solution compared to the reference product. While the reference product forfeits refrigeration post a stint at room temperature, the SB17 prefilled syringe graciously allows a return to refrigeration within a month of room temperature storage, not only unraveling enhanced flexibility but also curbing potential wastage.
However, amidst the crescendo of innovation, a discordant note echoes in the form of hurdles obstructing the uptake of ustekinumab biosimilars. Healthcare professionals’ apprehensions stand as a looming barrier, rooted in the complexities inherent to the biologic manufacturing process. The inherent variability within this process can birth discrepancies not only between originator biologics and biosimilars but also among distinct batches of the same biologic. The key to assuaging these concerns, as per the reviewers, lies in acknowledging the existence of variations between different batches of the reference product, a realization that could assuage the qualms of patients and healthcare professionals surrounding the efficacy and safety of biosimilars. Furthermore, the publication of additional real-world evidence in extrapolated indications emerges as a beacon of hope, fostering confidence in ustekinumab biosimilars and paving the path for their wider embrace.
In conclusion, the unveiling of SB17 and its symphony of evidence not only ushers in a new era of efficacy and safety in immunotherapy but also paints a canvas of patient-centric care and convenience. As the melody of innovation continues to reverberate, it is imperative to harmonize the discordant notes, surmount the barriers, and orchestrate a future where biosimilars seamlessly integrate into the tapestry of patient care, ensuring a crescendo of improved outcomes and enhanced experiences.
Takeaways:
– SB17, a ustekinumab biosimilar, showcases comparable efficacy and safety for psoriasis and psoriatic arthritis, offering an enhanced patient experience.
– The lower immunogenicity profile of SB17 compared to the ustekinumab originator underscores its potential in mitigating clinical consequences.
– The mechanism of action of SB17, targeting the p40 subunit of IL-12 and IL-23, lays the groundwork for extrapolation to various immune-mediated inflammatory diseases.
– Enhanced patient experience features of SB17, such as a streamlined drug administration process and improved storage flexibility, set a new standard in patient-centric care.
Tags: immunotherapy
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