
==== Front
Dermatol Ther (Heidelb)
Dermatol Ther (Heidelb)
Dermatology and Therapy
2193-8210
2190-9172
Springer Healthcare Cheshire

39147994
1253
10.1007/s13555-024-01253-6
Review
Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis
Yilmaz Orhan 1
http://orcid.org/0000-0003-0404-0870
Torres Tiago torres.tiago@outlook.com

23
1 https://ror.org/010x8gc63 grid.25152.31 0000 0001 2154 235X College of Medicine, University of Saskatchewan, Saskatoon, SK Canada
2 https://ror.org/043pwc612 grid.5808.5 0000 0001 1503 7226 Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
3 grid.5808.5 0000 0001 1503 7226 Department of Dermatology, Centro Hospitalar Universitário Do Porto, Largo Do Prof. Abel Salazar, S/N, 4099-001 Porto, Portugal
15 8 2024
15 8 2024
9 2024
14 9 23932406
15 7 2024
5 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase 2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

Keywords

Atopic dermatitis
APG777
IMG-007
Dupilumab
Lebrikizumab
Extended half-life antibodies
Immune modulation
issue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2024
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pmcKey Summary Points

Current management strategies for AD include topical treatments like corticosteroids, calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase (PDE) 4 inhibitors, which can be inadequate for severe cases, and systemic therapies like small molecules and biologics that offer significant advancements.	
JAK inhibitors effectively reduce AD symptoms but come with safety concerns and require daily oral administration.	
Monoclonal antibodies such as dupilumab, tralokinumab, and lebrikizumab target key inflammatory pathways but have burdensome frequent dosing schedules.	
Extended half-life antibodies, like APG777 and IMG-007, are engineered for prolonged circulation, allowing for reduced dosing frequency while maintaining efficacy.	
These novel biologics have the potential to improve patient adherence and reduce healthcare burdens, though long-term studies are needed to confirm their safety and efficacy.	

Introduction

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that affects millions of individuals worldwide, significantly impacting both physical health and quality of life. Characterized by intense pruritus and eczematous lesions, AD often manifests early in life and follows a course marked by periods of flare-ups and remission [1]. The prevalence of AD has increased over recent decades, especially in industrialized countries, highlighting the urgent need for effective and sustainable treatment options [2].

The pathogenesis of AD is complex and multifactorial [1, 3]. Epidermal barrier disruption, immune dysregulation (cutaneous and systemic), and disordered microbiome are thought to be the mechanistic drivers of the disease, interacting with each other in a self-amplifying loop. Skin barrier dysfunction is central to its development, allowing allergens and microbes to penetrate and trigger an immune response. This leads to the activation of T helper (Th) 2-dominant immune pathways, resulting in the production of cytokines such as interleukin (IL)-4, IL-13, and IL-31, which drive inflammation and pruritus. Additionally, the involvement of Th1, Th17, and Th22 pathways in chronic AD underscores the disease’s intricate immunologic landscape [1, 3]. Changes in the skin microbiome, particularly increased Staphylococcus aureus colonization, exacerbate skin barrier dysfunction and immune dysregulation, creating a feedback loop that perpetuates skin inflammation and AD clinical manifestation (Fig. 1) [1, 3].Fig. 1 Cellular and molecular pathophysiology of AD. AD atopic dermatitis, APC antigen-presenting cell, IDEC inflammatory dendritic epidermal cell, IFN interferon, IL interleukin, ILC2 innate lymphoid type-2 cell, OX40L OX40 ligand, Th T helper. Image retrieved from Guttman-Yassky et al. 2024 [37]. Licensed under a Creative Commons Attribution-Non-commercial 4.0 International License. License statement: this image is licensed under a Creative Commons Attribution-Non-commercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution, and reproduction in any medium or format, as long as appropriate credit is given to the original author(s) and the source, and a link to the Creative Commons license is provided. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ (Accessed on 3 August 2024)

Current management strategies for AD include a variety of topical and systemic therapies aimed at reducing inflammation, improving skin barrier function, and alleviating symptoms. Topical treatments, such as corticosteroids, calcineurin inhibitors, and the US Food and Drug Administration (FDA)-approved topical Janus kinase (JAK) inhibitor and topical phosphodiesterase (PDE) 4 inhibitors, are often first-line therapies but can be inadequate for moderate to severe cases. Systemic therapies, including advanced targeted treatments like small molecules and biologics, have provided significant advancements in AD management [1, 3].

Small molecules, such as JAK inhibitors, offer the benefit of oral administration and have proven effective in reducing AD symptoms by targeting specific signaling pathways [4]. However, their use is often limited by safety concerns, including potential adverse effects on the hematologic and immune systems [5]. Furthermore, the necessity for daily oral administration can be burdensome for patients, affecting adherence and overall treatment success [6].

Biologic therapies, particularly monoclonal antibodies (mAb), have revolutionized the treatment landscape for moderate to severe AD [7]. These biologics are highly targeted, offering precise intervention at key targets in the inflammatory cascade. For instance, dupilumab, an IL-4 receptor alpha (IL-4Rα) antagonist, as well as tralokinumab and lebrikizumab, both IL-13 inhibitors, have demonstrated substantial efficacy in reducing AD symptoms and improving quality of life [8]. Despite these benefits, the frequent dosing schedules required for biologics can be a significant drawback. Many biologics necessitate biweekly or monthly injections, posing a burden to patients and potentially impacting adherence [9]. Given these challenges, there is a compelling need to explore new therapeutic strategies that retain the benefits of advanced targeted therapies while addressing their limitations.

One potential approach is the development of novel mechanisms of action, such as the OX40-OX40L [10] and IL-22R antagonists [11], or even bispecific antibodies that target multiple cytokine pathways involved in AD [11, 12].

Another promising strategy is the development of extended half-life antibodies. These innovative biologics utilize known mechanisms of action but are engineered for prolonged circulation, allowing for less frequent dosing [13]. For example, by increasing their binding affinity to the neonatal Fc receptor (FcRn), these antibodies achieve extended half-lives, reducing the need for frequent administration without compromising efficacy [14].

Extended half-life antibodies may represent a significant advancement in biologic therapy for AD, offering the potential for sustained therapeutic effects with reduced dosing frequency. This narrative review explores the latest advancements in extended half-life antibodies for AD, focusing on their mechanisms of action, clinical efficacy, safety profiles, and the future directions of this promising therapeutic approach. A review of the published literature was conducted (up until June 2024) using the PubMed and Medline databases, published abstracts and virtual presentations from scientific meetings, data from industry press releases, and results published on ClinicalTrials.gov.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Development of Extended Half-life Antibodies

The development of extended half-life antibodies marks a significant advancement in biologic therapies [15]. This process involves sophisticated engineering to enhance the pharmacokinetic properties of antibodies, ensuring prolonged circulation in the bloodstream and reducing the frequency of administration needed for therapeutic efficacy [15].

There are several engineering strategies to extend the half-life of antibodies, including pegylation, glycoengineering, protein engineering, and fragment crystallizable (Fc) region modification.

Pegylation, the first successful technology used to extend the half-life of biologics, has been applied in clinical medicine for over 25 years. This technique involves attaching polyethylene glycol (PEG) chains to the antibody, which shields the antibody from proteolytic enzymes and immune clearance, thereby extending its half-life. However, the process of pegylation must be carefully optimized to avoid impairing the antibody’s binding affinity and functionality [16].

Glycoengineering involves adding sugar molecules to the antibody structure, which significantly impacts its half-life. The process alters glycosylation patterns to enhance FcRn binding or reduce immune system recognition and clearance, thereby improving the stability and longevity of the antibody in the body [15, 17, 18].

Protein engineering employs advanced techniques to design antibodies with optimized structures. These include amino acid substitutions, domain swapping, and other modifications that enhance the antibody’s stability and half-life [15]. The goal is to maintain high affinity for target antigens while improving pharmacokinetic properties [15, 18].

Finally, Fc region modification involves altering the Fc region of an antibody, which plays a crucial role in determining its half-life. By modifying the Fc region, the antibody’s affinity for the neonatal Fc receptor (FcRn) is increased. This receptor recycles antibodies and protects them from lysosomal degradation [13]. Enhanced binding to FcRn results in a longer half-life, allowing antibodies to remain active in the circulation for extended periods [13, 15].

Ravulizumab (Ultomiris®) was approved by the FDA in 2018 for paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive [19]. It was the first antibody with engineered Fc variants designed for an improved serum half-life [13]. It demonstrated a fourfold longer frequency of administration compared to eculizumab (Soliris®) [13]. Many pharmaceutical companies are currently developing extended half-life antibodies by improving the pH-dependent FcRn binding profiles, including for chronic conditions such as atopic dermatitis.

Extended Half-life Antibodies for Atopic Dermatitis

Extended half-life antibodies being developed for atopic dermatitis utilize well-established mechanisms of action, such as IL-13 and OX40 pathway inhibition. These therapies incorporate advanced antibody engineering to optimize half-life and other properties, aiming to enhance therapeutic efficacy and patient convenience.

APG777

APG777 is a novel, humanized IgG1 mAb developed by Apogee Therapeutics (USA). It targets IL-13, with high affinity, a key cytokine involved in AD, asthma, and various other inflammatory conditions and the main driver of the Th2 inflammatory axis [20]. This antibody features a unique amino acid modification in its Fc region, which extends its half-life, thereby reducing the frequency of dosing needed for therapeutic effectiveness [20].

In preclinical studies involving female cynomolgus monkeys, a single dose of 3 mg/kg of APG777 administered intravenously and subcutaneously exhibited an average half-life of 27.6 days and a clearance rate of 1.45 mL/day/kg. It also showed high subcutaneous bioavailability of 81.22% and a volume of distribution at steady-state of 55.65 mL/kg (Table 1). These properties suggest that APG777 can potentially enable less frequent dosing compared to existing therapies [20, 21].Table 1 Clinical trials investigating extended half-life antibodies for the treatment of AD

Treatment	Trial	Study design	Endpoints	Main results disclosed	Main adverse events	Trial status	
APG777

(IL-13 antagonist mAb)

	Preclinical [20, 21]	Female cynomolgus monkeys

Single dose of 3 mg/kg administered intravenously and subcutaneously

Blood samples collected serially over a span of 2160 h post-dose

	N/A	Average half-life of 27.6 days and a clearance rate of 1.45 mL/day/kg

High subcutaneous bioavailability of 81.22% and a volume of distribution at steady-state of 55.65 mL/kg

	N/A	Completed	
Phase I [21–23]	40 healthy adult volunteers, divided into three SAD and two MAD cohorts

Dosing: 300 mg, 600 mg, and 1200 mg, and high concentration formulation of 180 mg/mL

	To optimize exposure levels in 16-week induction and be dosed once every 3 or 6 months in maintenance	Interim results

 Half-life of approximately 75 days

 Sustained inhibition of key AD biomarkers pSTAT6 and TARC for approximately 3 months (inhibition still ongoing at time of the data cut)

 Dose-proportional increases in serum concentrations and key parameters (e.g., Cmax, AUC)

	Well tolerated in both single doses up to 1200 mg and multiple doses of 300 mg

TEAEs included vascular access site pain and bruising, headache, with 60% of participants experiencing at least one TEAE and 15% experiencing a drug-related adverse event

No SAEs or grade 3 TEAEs

	Ongoing	
Phase IIa/IIb (NCT06395948) [22, 23, 24]	16-week, two-part, randomized, multicenter, placebo-controlled, double-blind, proof-of-concept study

Combined typical phase 2a and 2b portions into single protocol

Phase IIa—110 patients randomized 2:1, APG777 or placebo, with APG777 administered at 720 mg at weeks 0 and 2, followed by 360 mg at weeks 4 and 12. Continue with maintenance dosing every 3 to 6 months

Phase IIb—360 patients randomized 1:1:1:1 to high, medium, or low doses of APG777 versus placebo

	Primary

 Change in EASI score from baseline to week 16

Secondary

 TEAEs up to week 106

 EASI 50, 75, 90, 100 through week 16 and at week 52

 IGA 0/1 through week 16 and at week 52

 Change in BSA involved through week 16 and at week 52

 Cmax, and tmax up to week 106

 AUC and AUC0–tau up to week 106

 Predose serum, and serum concentrations up to week 106

	N/A	N/A	Recruiting	
IMG-007 (nondepleting OX40R antagonist mAb)	Phase I (NCT05353972) [25, 26, 28]	44 healthy adults

Double-blind, randomized, placebo-controlled, sequential ascending SAD

	Primary

 TEAEs up to 127 days

Secondary

 Cmax, and tmax up to 127 days

 AUC, and AUC0–tau up to 127 days

 Half-life up to 127 days

 Incidence of ADA after infusion up to 127 days

	31-day half-life at anticipated therapeutic dose levels

Single administration sustains target serum concentration for about 12–18 weeks

	No reports of fever or chills	Completed	
Phase Ib/2a (NCT05984784) [25, 29, 38]	13 patients

Double-arm, open-label

Patients assigned via sequential assignment to 1 of 2 treatment arms, including a 300 mg or 600 mg dose of IMG-007, both to be administered intravenously 3 times over a 4-week period

Screening period of up to 5 weeks, 12-week treatment period, and 12-week follow-up period

	Primary

 AEs and TEAEs at baseline and week 24

Secondary

 Pharmacokinetic characterization at baseline and week 24

 EASI at baseline and week 12

	EASI was 23%, 29%, 47%, 66%, 68%, 77%, and 87% at weeks 1, 2, 4, 8, 12, 16, and 20, respectively

By week 20, 69% of patients achieved EASI-50, 54% achieved EASI-75, and 31% achieved EASI-90

	No SAEs, no AEs leading to treatment discontinuation, and no TEAEs, with no incidents of fever or chills	Terminated	
Phase I (NCT06304740) [30]	24 healthy adult volunteer participants

Double-blind, randomized, placebo-controlled

Subcutaneous dose

	Primary

 AEs up to week 18

Secondary

 Cmax, tmax, and AUC0–tau up to week 18

	N/A	N/A	Active, not recruiting	
APG990 (OX40L antagonist mAb)	Preclinical [32]	N/A	N/A	N/A	N/A	Ongoing	
APG222 (IL-13/OX40L antagonist mAb)	Preclinical [32]	N/A	N/A	N/A	N/A	Ongoing	
ADA anti-drug antibody, AE adverse event, AUC area under the concentration–time curve, AUC0–tau AUC over the dosing interval, Cmax maximum concentration, MAD multiple-ascending dose, N/A not applicable, SAE severe adverse event, SAD single-ascending dose, TEAE treatment-emergent adverse event, tmax time to reach Cmax

For comparison, lebrikizumab, another IL-13 mAb, demonstrated an average half-life of 18.0 days and a clearance rate of 2.93 mL/day/kg in the same population. It displayed similar absorption characteristics with a bioavailability of 75.70% and a volume of distribution at steady-state of 52.10 mL/kg [20, 21]. Moreover, in head-to-head preclinical studies, APG777 demonstrated equivalent or better potency in inhibiting IL-13 signaling compared to lebrikizumab [22].

Interim clinical data from the phase 1 study of APG777 in 40 healthy adult volunteers demonstrated half-life of approximately 75 days [21–23]. This prolonged half-life supports the possibility of administering APG777 every 3–6 months (Table 1) [23].

The single-dose administration of APG777 demonstrated significant and sustained inhibition of key AD biomarkers, specifically pSTAT6 and TARC, for around 3 months, with ongoing inhibition observed at the data cutoff. The safety profile of APG777 was favorable, aligning with the established safety profile of the IL-13 inhibitors class. The drug was well tolerated in both single doses up to 1200 mg and multiple doses of 300 mg, indicating a robust safety margin. Common treatment-emergent adverse events (TEAEs) included headache and vascular access site pain and bruising. Sixty percent of participants experienced at least one TEAE and 15% experienced a drug-related adverse event. Importantly, no severe adverse events (SAEs) or grade 3 TEAEs were reported [23].

In April 2024, the phase 2 trial of APG777 in patients with moderate-to-severe AD (NCT06395948) was initiated. This 16-week, randomized, placebo-controlled study is designed to combine the typical phase 2a and 2b portions into a single protocol, potentially accelerating the development timeline [22, 24]. There are currently no results available, and recruitment is ongoing [24].

Part A (phase IIa) of the trial will enroll approximately 110 patients randomized 2:1 to receive APG777 or placebo, with APG777 administered at 720 mg at weeks 0 and 2, followed by 360 mg at weeks 4 and 12. Patients benefiting from the treatment will continue with maintenance dosing every 3–6 months (Table 1).

Part B (phase IIb) involves approximately 360 patients randomized 1:1:1:1 to high, medium, or low doses of APG777 versus placebo. The primary endpoint for both parts of the study is the mean percentage change in Eczema Area and Severity Index (EASI) score from baseline to week 16 (Table 1) [22, 24].

Furthermore, the evaluation of APG777 is expected to extend to other immune-mediated indications, including asthma, alopecia areata, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria, eosinophilic esophagitis, and prurigo nodularis [22].

IMG-007

IMG-007, developed by Inmagene (USA), is a nondepleting humanized IgG1 mAb that specifically binds to the OX40 receptor [25, 26]. Its Fc region has been engineered to have a silenced antibody-dependent cellular cytotoxicity (ADCC) function, preventing T cell depletion, and to extend its half-life [25, 26]. OX40 is a co-stimulatory receptor primarily found on activated T cells, and the interaction between OX40-OX40L is crucial for T cell activation, expansion, and survival, playing a significant role in the pathogenesis of AD (Fig. 1) [10]. In nonclinical studies, IMG-007 effectively and completely inhibited the signaling between OX40 and OX40L [26, 27].

In a previous phase I single-dose study involving 44 healthy adults (NCT05353972), IMG-007 exhibited a favorable safety profile with no instances of fever or chills, consistent with its abolished ADCC function [25, 28]. The study also showed IMG-007 had a slow clearance and a 31-day half-life at anticipated therapeutic doses, supporting a 12-week dosing interval for induction therapy [25]. At the projected therapeutic dose levels, a single administration of IMG-007 sustains the target serum concentration for about 12–18 weeks (Table 1). This suggests the possibility of less frequent dosing for maintenance in AD treatment [25, 26, 28].

The phase 1b/2a double-arm, open-label trial (NCT05984784) assessed the safety, pharmacokinetics, and efficacy of IMG-007 in adults with moderate-to-severe AD who were unresponsive or intolerant to topical therapies, including those who had previously used systemic agents, including biologics [25]. During the study, participants were not allowed to use topical or systemic AD medications. Patients received three intravenous infusions of 300 mg IMG-007 over 4 weeks (at baseline, week 2, and week 4) and were monitored for up to 24 weeks. Key endpoints included safety and percent change in EASI [25]. Thirteen patients from six centers in the USA and Canada participated in the study. Baseline characteristics included a mean EASI of 29.5 and a mean body surface area (BSA) of 52.0%, with 61.5% of patients having an IGA of 3, and 38.5% with IGA of 4. Treatment with IMG-007 resulted in rapid and significant improvements in EASI scores starting at week 1 and continuing through week 20. The mean percent improvement in EASI was 23%, 29%, 47%, 66%, 68%, 77%, and 87% at weeks 1, 2, 4, 8, 12, 16, and 20, respectively. By week 20, 69% of patients achieved EASI-50, 54% achieved EASI-75, and 31% achieved EASI-90 [25, 28]. There were no SAEs, no AEs leading to treatment discontinuation, and no TEAEs, with no incidents of fever or chills (Table 1) [25, 29].

Another phase I trial is currently being conducted in AD using a subcutaneous formulation of IMG-007 (NCT06304740) (Table 1) [30].

IMG-007 is also being evaluated in adult patients with alopecia areata (AA) (NCT06060977), with initial data anticipated in Q4 2024 [31].

Other Extended Half-life Antibodies Being Developed for Atopic Dermatitis

APG990 is designed to target OX40L, while APG222 is developed to target both IL-13 and OX40L [32]. Both antibodies are currently in the early phases of development. They have been optimized to bind with high affinity to FcRn, extending their presence in the bloodstream and potentially reducing the frequency of required doses [32].

APG990 is expected to be initiated in a phase I trial in healthy volunteers in the second half of 2024, with initial data on pharmacokinetics (PK) and safety anticipated in 2025 [32].

APG222 (PR012) is currently in the early phases of development (Table 1) [32].

Discussion

Extended half-life antibodies may represent a significant advancement in the treatment of AD. Utilizing well-established mechanisms of action, these therapies incorporate advanced antibody engineering to optimize their half-life and other properties [13]. This offers substantial benefits in terms of adherence, dosing convenience, clinical outcomes, and healthcare resource utilization.

To date, two agents are in phase II trials with available promising results: APG777, targeting the IL-13 pathway, and IMG-007, targeting the OX40 pathway.

One of the primary advantages of extended half-life antibodies for AD is the potential for improved patient adherence. Traditional biologic treatments for AD often require biweekly or monthly injections, which can be burdensome for patients (particularly those with needle phobia) and potentially leading to missed doses. For instance, APG777’s extended half-life suggests it could be administered every 3–6 months [23], while IMG-007 demonstrated a half-life of 31 days, supporting a dosing interval of every 12 weeks for induction therapy [25]. This represents a significant reduction compared to the more frequent 2- to 4-week dosing schedules of existing treatments, such as dupilumab, tralokinumab, or lebrikizumab. Even the biologics targeting the OX40-OX40L pathway currently in development, such as amlitelimab and rocatinlimab, require dosing schedules every 4 weeks [10]. This convenience is likely to enhance adherence, as patients are less likely to miss doses owing to the less frequent treatment regimen [33].

This extended dosing regimen may not only improve adherence but also reduce the logistical burden on both the patients and on healthcare systems. Fewer hospital visits for drug dispensation and medical appointments are particularly beneficial for patients with limited access to medical facilities or those who experience difficulty in maintaining frequent appointments. This is especially relevant in healthcare systems with limited capacity or in rural areas where access to specialized care is limited. By optimizing resource utilization, these therapies can enhance the efficiency of healthcare delivery, ensuring that more patients receive the care they need without overwhelming healthcare facilities.

Finally, extended half-life antibodies may also have significant economic implications. The overall cost-effectiveness may improve through reduced administration frequency and lower healthcare utilization, as fewer injections and clinic visits can translate into substantial savings in healthcare costs over time [34].

Despite these promising results, we are still in the very early stages of development for these novel therapeutics. Long-term studies are essential to fully understand the safety and efficacy profile of extended half-life antibodies in the treatment of AD. While initial trials, such as those for APG777 and IMG-007, have shown promising results, large phase III and long-term clinical trials will be crucial for monitoring long-term outcomes and identifying any potential late-onset adverse effects.

The field of antibody engineering continues to evolve, with new techniques being developed to further enhance the properties of therapeutic antibodies. Innovations such as bispecific antibodies, antibody–drug conjugates, and novel Fc modifications hold promise for creating even more effective treatments with extended half-lives and enhanced therapeutic profiles [35, 36]. For instance, APG990, which targets OX40L, and APG222, a dual inhibitor of IL-13 and OX40L, may offer more comprehensive treatment options for AD and other inflammatory conditions.

Conclusion

The positive preliminary trial results for APG777 and IMG-007 underscore their potential as future treatment options for AD, improving patient quality of life and reducing the burden on healthcare systems. Continued research and development in this field will likely lead to further improvements and broader applications, ultimately enhancing the quality of life for patients with AD and other chronic inflammatory diseases.

Author Contributions

Orhan Yilmaz and Tiago Torrez contributed equally to the preparation of this review. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Funding

No funding or sponsorship was received for this study or publication of this article.

Data Availability

Data availability is not applicable to this article as no new data was created or analyzed in this study. This is a narrative review, and all sources of information are cited appropriately in the manuscript.

Declarations

Conflict of Interest

Orhan Yilmaz has nothing to disclose. Tiago Torres has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Amgen, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz and UCB. Tiago Torres is an Editorial Board member of Dermatology and Therapy. Tiago Torres was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
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