Extended Half-Life and Long-Acting Biologics for the Treatment of Psoriasis
Explore the biologic rationale, emerging clinical candidates, and key unanswered questions surrounding extended half-life therapies for psoriatic disease.
Key Takeaways
- Extended half-life therapies may improve patient adherence by reducing injection burden, minimizing treatment fatigue, and simplifying long-term disease management.
- Fc-region engineering enhances interaction with the neonatal Fc receptor (FcRn), promoting antibody recycling and extending biologic half-life.
- Investigational agents are assessing whether prolonged drug exposure can deliver deeper remission and sustained control of both skin and joint manifestations.
- Important unanswered questions remain regarding long-term safety, potential wear-off effects, adverse event management, and comparative effectiveness versus currently approved biologics.
Over the last two decades, substantial advances have been made in the treatment of psoriasis. These therapeutic advances are largely due to the discovery and selective inhibition of the IL-23/IL-17 signaling axis in mature psoriatic plaques.1 Newer biologic medicines can achieve complete skin clearance (PASI 100) in approximately two-thirds of treated patients at one year, making psoriasis one of the most effectively treated immune-mediated inflammatory diseases.
Despite these advances, important unmet needs remain for patients living with chronic psoriasis. Biologic therapies can impose a substantial treatment burden because of high cost, variable insurance or health-system access, and the need for intravenous or subcutaneous administration. Long-term disease control also required ongoing dosing to maintain improvement in both skin and joint symptoms. In addition, some patients who initially respond well to biologic therapy experience a gradual loss of clinical benefit over time, commonly referred to as secondary treatment failure.
The desire for improved patient experience and disease control has prompted research efforts to build upon the success of highly effective psoriasis biologics, such as risankizumab and bimekizumab.2 These efforts include novel biologic treatment strategies, such as higher-dose injections, improved target binding, and antibody modifications designed to extend drug half-life.3 Collectively, these next-generation approaches aim to increase pharmacokinetic durability, reduce injection frequency, and potentially enhance disease control or remission. This article summarizes the biologic rationale, emerging clinical candidates, and key unanswered questions surrounding extended half-life therapies for psoriatic disease.
The Underlying Science of Extended Half-Life Biologics
The half-life of a medication (or t1/2) is the amount of time for the concentration of an administered drug to be reduced by 50%. It estimates the durability of a medication in the body and, therefore, its potential therapeutic benefit for an underlying condition. There are multiple ways to extend the half-life of a product, such as pegylation, glycosylation, albumin-binding modifications, and bioengineering of the antibody’s Fc region (eg, YTE amino acid substitutions).
Fc-region engineering can enhance antibody binding to the neonatal Fc receptor (or FcRn) under acidic endosomal conditions, promoting antibody recycling and reducing lysosomal degradation.3 In some settings, this approach can substantially extend the half-life of monoclonal antibodies by several fold.4 Coupling this novel technology with additional enhancements such as higher-dose injections and improved cytokine binding represents a viable research strategy for potentially achieving improved disease control with fewer injections.
Clinical Testing in Dermatology and Psoriasis Cohorts
Diverse clinical trial programs are underway evaluating the safety and efficacy of extended half-life biologics for the treatment of several inflammatory conditions, including plaque psoriasis. These investigational agents for psoriasis primarily target IL-17A/F or IL-23p19 based on the prior success of similar FDA-approved treatments but also include novel targets such as TNF-like ligand 1A (TL1A).5 An overview of these agents is summarized in Table 1.
Ongoing studies of these investigational agents are evaluating whether extended half-life strategies can provide deeper, more durable psoriasis control with fewer administrations. These clinical trial programs are also assessing optimal dosing schedules and whether adequate skin and/or joint control can be maintained with as little as one injection per year. Early results from these clinical trials will also be important for assessing tolerability and safety in light of their long-acting mechanism. At present, complete clinical data for ongoing studies are unavailable, and direct comparisons with established IL-17 and IL-23 inhibitors are not yet available.
Future Directions
The value proposition for a nanobody or monoclonal antibody with an extended half-life goes far beyond improved disease control and a reduced injection schedule. These kinds of minimal dosing regimens could also impact medication adherence in patients with chronic disease who may experience injection fatigue, anxiety, or difficulty performing subcutaneous injections. The economic implications also warrant careful evaluation, particularly given the high acquisition costs and administrative burden associated with biologic therapies.
However, several important research questions must be addressed in ongoing clinical trials, including the overall safety profile compared to related products with a similar biologic target and the possibility of pharmacokinetic troughs or a “wear-off” effect preceding the next scheduled dose. New disease management and adverse event mitigation strategies may also need to be developed if patients experience a clinically relevant adverse event (eg, candidiasis with blockade of IL-17A/F),6-8 unplanned pregnancy, or the need for invasive medical interventions or procedures shortly after the administration of a long-acting psoriasis medication.
Nevertheless, half-life extension technologies are a compelling advancement in patient-centered clinical care and shared-decision making. Their prospective impact on disease remission is of considerable interest to patients and clinicians. These agents represent an important therapeutic innovation at a time when existing highly effective systemic therapies are increasingly difficult to differentiate and marginal gains in global efficacy assessments are harder to achieve.
1. Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201(6):1605-1613. https://doi.org/10.4049/jimmunol.1800013
2. Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2021;4(4):CD011535. https://doi.org/10.1002/14651858.CD011535.pub4
3. Ko S, Jo M, Jung ST. Recent achievements and challenges in prolonging the serum half-lives of therapeutic IgG antibodies through Fc engineering. BioDrugs. 2021;35(2):147-157. https://doi.org/10.1007/s40259-021-00471-0
4. Torres T, Blauvelt A. High-dose, extended half-life IL-23 inhibitors: the next big step in psoriasis care? Dermatol Ther (Heidelb). 2026;16(4):1841-1845. https://doi.org/10.1007/s13555-026-01707-z
5. Siegel M, Zhu E, Rios D, et al. Discovery, development, and characterization of SPY002 and SPY072, two novel extended half-life monoclonal antibodies targeting TL1A: in vitro properties, in vivo pharmacology, pharmacokinetics, and preclinical safety. mAbs. 2026;18(1):2670848. https://doi.org/10.1080/19420862.2026.2670848
6. McInnes IB, Coates LC, Mease PJ, et al. Sonelokimab, an IL-17A/IL-17F-inhibiting nanobody for active psoriatic arthritis: a randomized, placebo-controlled phase 2 trial. Nat Med. 2025;31(12):4160-4171. https://doi.org/10.1038/s41591-025-03971-6
7. Schwarz CW, Näslund-Koch C, Zachariae C, et al. Adverse events and immune response in psoriasis patients receiving interleukin-17 inhibitors. Acta Derm Venereol. 2025;105:adv43685. https://doi.org/10.2340/actadv.v105.43685
8. Moon S, Choi HY, Choi YJ, Shin S. Clinical efficacy and safety profile of bimekizumab in psoriasis: a systematic review and meta-analysis of randomized controlled trials. Endocr Metab Immune Disord Drug Targets. Published online May 17, 2026. https://doi.org/10.2174/0118715303446173260506053451
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