New monoclonal antibodies in targeted therapy of allergic diseases

Introduction

Allergic diseases (ADs) represent a global healthcare challenge, imposing a significant burden on medical resources due to their increasing prevalence, chronic nature, and often severe course. They rank as the fourth most common chronic disease worldwide [1]. Currently, approximately 30-40% of the global population suffers from various forms of allergy. Preliminary forecasts suggest that by 2050, every second person on Earth will have at least one AD [2].

Despite the progress achieved in the treatment of ADs with symptomatic pharmacotherapy and the use of allergen-specific immunotherapy, there remains a significant unmet need for the development of new treatment modalities [3]. Unlike traditional approaches, monoclonal antibodies (mAbs) can precisely target key components of the allergic inflammation cascade, thereby reducing the risk of adverse effects (AEs) and improving clinical outcomes. The application of mAbs in the therapy of ADs has expanded considerably over the past two decades [4]. Although numerous mAbs have been developed, only a few have so far received approval for clinical use in the treatment of ADs, including in the Russian Federation (RF) (Table 1) [5-10].

Table 1. Monoclonal antibodies registered in the Russian Federation for the treatment of allergic diseases

In recent years, promising results from clinical trials on the efficacy and safety of new mAbs have been obtained, and the indications for already established drugs have been expanded [11-12].

Objective

To briefly summarize data on the efficacy and safety of new mAbs that have successfully completed late-stage clinical trials (Phase II or III) within the last 7 years or received U.S. Food and Drug Administration (FDA) approval in 2024-2025 for the treatment of certain allergic diseases.

Materials and Methods

A search for English-language articles published up to May 2025 was conducted in PubMed and Google Scholar using the keywords: "biologics", "monoclonal antibodies", "asthma", "atopic eczema", "allergic rhinitis", "eosinophilic esophagitis", "food allergy", and "chronic spontaneous urticaria". A manual search of the reference lists of the retrieved articles was performed to identify additional relevant citations.

Bronchial Asthma

According to the 2025 GINA (Global Initiative for Asthma) guidelines, four classes of biologics are currently used for the treatment of severe asthma: anti-IgE antibodies; agents targeting the IL-5 pathway; IL-4 receptor (IL-4R) blockers; and thymic stromal lymphopoietin (TSLP) inhibitors [13]. Biologic therapy has proven effective in controlling symptoms, improving lung function, reducing the need for systemic corticosteroids, and decreasing the frequency of exacerbations and healthcare utilization [14]. Despite these advances, many patients continue to experience asthma exacerbations, and the majority fail to achieve full disease control [15].

Ultra-Long-Acting Monoclonal Antibodies
Currently available mAbs for asthma require administration every 2-8 weeks, which may impact treatment adherence [16].
Depemokimab is a mAb characterized by an ultra-long duration of action, allowing for administration at 6-month intervals. It targets IL-5R, which is responsible for the growth, differentiation, activation, and survival of eosinophils and influences the activity of airway inflammatory cells. Results from two multicenter, randomized, double-blind, placebo-controlled trials (MRDBPCTs), the Phase III SWIFT-1 and SWIFT-2 studies, showed that depemokimab statistically significantly reduced the annualized exacerbation rate in patients with severe eosinophilic asthma compared to placebo. In SWIFT-1, the rate was 0.46 (95% CI: 0.36-0.58) for depemokimab vs. 1.11 (95% CI: 0.86-1.43) for placebo (rate ratio [RR] 0.42; 95% CI: 0.30-0.59, p<0.001); in SWIFT-2, it was 0.56 (95% CI: 0.44-0.70) vs. 1.08 (95% CI: 0.83-1.41) (RR 0.52; 95% CI: 0.36-0.73, p<0.001). The proportion of patients with any AEs was similar between groups in both studies [17]. In early 2025, the FDA accepted the licensing application for depemokimab for the treatment of severe asthma with an eosinophilic phenotype in adults and adolescents aged ≥12 years [18].

Anti-IL-13
Lebrikizumab is a mAb that blocks IL-13, a pleiotropic cytokine involved in key pathophysiological processes of asthma, including IgE synthesis, airway remodeling, smooth muscle hyperplasia, bronchial hyperreactivity, and inflammatory cell activation. Although three large Phase III MRDBPCTs (LAVOLTA I, LAVOLTA II, and ACOUSTICS) did not demonstrate a consistent reduction in asthma exacerbations in the overall population, a post-hoc analysis revealed that in patients with blood eosinophilia ≥300 cells/µL and ≥1 exacerbation in the previous year, lebrikizumab significantly reduced the rate of new exacerbations: by 38% at the 125 mg dose and 41% at the 37.5 mg dose in adults, and by 59% and 64%, respectively, in adolescents, compared to placebo. Most AEs were mild or moderate in severity and did not lead to treatment discontinuation [19].

Anti-IL-33/ST2
IL-33 is an alarmin released by damaged airway epithelium that activates inflammatory cells, triggering the release of pro-inflammatory cytokines [20].
Itepekimab is a novel anti-IL-33 mAb. In a Phase II MRDBPCT, adult patients with moderate-to-severe asthma received itepekimab, dupilumab, their combination, or placebo for 12 weeks. The percentage of patients with asthma exacerbations was lower in all active treatment groups compared to placebo: 22% in the itepekimab group, 27% in the combination group, and 19% in the dupilumab group, versus 41% in the placebo group. The corresponding odds ratios (ORs) compared to placebo were: 0.42 (95% CI 0.20-0.88; p=0.02) for itepekimab, 0.52 (95% CI 0.26-1.06; p=0.07) for combination therapy, and 0.33 (95% CI 0.15-0.70) for dupilumab. The incidence of AEs was similar across all four groups [21].
Tozorakimab is another IL-33 antagonist evaluated in the Phase IIa DBPC FRONTIER-3 trial in patients with uncontrolled moderate-to-severe early-onset asthma, 76.2% of whom had blood eosinophil levels <300 cells/µL. The drug did not show a significant improvement in FEV1 in the overall population at week 16 compared to placebo; however, patients with ≥2 exacerbations in the previous year who received the 600 mg dose showed improved lung function, suggesting potential efficacy of tozorakimab in non-eosinophilic patients—a group less responsive to currently approved biologics [22].
Astegolimab is a mAb that selectively blocks the IL-33 receptor ST2. In the Phase IIb MRDBPCT ZENYATTA, astegolimab reduced the annualized asthma exacerbation rate compared to placebo by 43% (p=0.005), 22% (p=0.18), and 37% (p=0.01) at doses of 490 mg, 210 mg, and 70 mg, respectively, in the overall population of patients with any eosinophil level. In patients with low eosinophil counts (<300 cells/µL), the reduction was 54% (p=0.002), 14% (p=0.48), and 35% (p=0.05), respectively. AEs were similar across groups. This indicates that inhibition of the IL-33/ST2 pathway can also effectively target pathogenic mechanisms in asthma patients without blood eosinophilia [20].

Atopic Eczema

Currently, mAbs approved for the treatment of atopic eczema (AE) target the suppression of IL-4 and IL-13 activity [23].

Anti-IL-4R
IL-4 and IL-13 play a crucial role in the pathogenesis of AE by stimulating Th2-cell differentiation, keratinocyte apoptosis, IgE production, and impairing the skin barrier through reduced expression of filaggrin, loricrin, and involucrin [24].
Rademikibart is a mAb targeting the IL-4 receptor α-subunit (IL-4Rα). In a Phase II MRDBPCT among adult patients with moderate-to-severe AE, previously naïve to IL-4Rα/IL-13 blockers, participants were randomized to receive various doses of rademikibart or placebo. By week 16, rademikibart therapy led to a significant reduction in the Eczema Area and Severity Index (EASI) score: by 63.0% (p=0.0007) with 300 mg every 2 weeks, 57.6% (p=0.0067) with 150 mg every 2 weeks, and 63.5% (p=0.0004) with 300 mg every 4 weeks, compared to placebo (-39.7%). The 300 mg doses administered every 2 and 4 weeks showed a significant clinical response: EASI-75 was achieved by 47.4% (p<0.0001) and 39.3% (p≤0.001) of patients, respectively, versus 12.5% in the placebo group, while EASI-90 was achieved by 24.6% (p<0.05) and 23.2% (p<0.05), respectively, versus 8.9% with placebo. The incidence of AEs was similar between rademikibart and placebo [25].
Stapokibart is another mAb targeting IL-4Rα. In a Phase III DBPC trial involving adult patients with moderate-to-severe AE, at week 16, 66.9% of patients receiving stapokibart achieved EASI-75 compared to 25.8% in the placebo group (p<0.0001), and an Investigator's Global Assessment (IGA) score of 0/1 with an improvement of ≥2 points was achieved by 44.2% vs. 16.1% (p<0.0001). The incidence of AEs was comparable between the two groups [26]. After the 16-week course, patients from both groups transitioned to stapokibart maintenance therapy. At week 52, EASI-75 was achieved by 92.5% of patients continuing stapokibart and 88.7% of those who switched from placebo to stapokibart; IGA 0/1 with a ≥2-point reduction was achieved by 67.3% and 64.2% of patients, respectively [27].

Anti-IL-13/IL-13R
Tralokinumab was the second mAb after dupilumab to receive FDA approval for the treatment of AE in patients aged ≥12 years [28]. Its mechanism of action involves blocking IL-13. Phase III clinical trials demonstrated significantly greater efficacy of tralokinumab compared to placebo in reducing signs and symptoms of the disease in patients with moderate-to-severe AE [29-31]. Real-world data showed that one year of tralokinumab treatment led to substantial patient improvement: the EASI score decreased from 15.0 (IQR: 10.20, 21.35) to 2.1 (IQR: 0.90, 4.85) (p<0.001); 68.5% and 33.3% of patients achieved EASI-75 and EASI-90, respectively. The median Dermatology Life Quality Index (DLQI) score decreased from 9.00 (IQR: 6.00, 13.75) at baseline to 1.00 (IQR: 0.00, 4.00) after one year of treatment (p<0.001). AEs were reported in <10% of patients and included eye disorders (conjunctivitis and blepharitis) and injection site reactions [32]. Tralokinumab may be effective in AE patients who do not respond to dupilumab treatment (particularly patients with head and neck involvement) [33-34].
Lebrikizumab is a mAb that also selectively binds IL-13. The ADvocate1 and ADvocate2 studies were Phase III DBPC trials evaluating the efficacy of lebrikizumab monotherapy in patients ≥12 years old with moderate-to-severe AE. During the 16-week induction period, all patients received lebrikizumab. Those who achieved EASI-75 or IGA response were re-randomized to receive lebrikumab every 2 weeks, every 4 weeks, or placebo. In the pooled data from both studies at week 52, the proportion of patients maintaining an IGA score of 0/1 with a ≥2-point improvement was 71.2% in the lebrikizumab every 2 weeks group, 76.9% in the every 4 weeks group, and 47.9% in the placebo group. A sustained EASI-75 response was recorded in 78.4%, 81.7%, and 66.4% of patients, respectively. Throughout the study period, 63.0% of patients receiving lebrikizumab reported any treatment-emergent AEs, with the majority (93.1%) being mild or moderate [35]. To date, lebrikizumab is the most recently FDA-approved drug for AE in patients ≥12 years [36].
Cendakimab has a similar mechanism of action, blocking IL-13. In a Phase II DBPC trial, participants with moderate-to-severe AE were randomized to receive cendakimab at various dosages or placebo. Administration of cendakimab 720 mg once weekly led to a greater change in EASI score (-84.4%) compared to the groups receiving 720 mg every 2 weeks (-76.0%) and 360 mg every 2 weeks (-78.9%) (difference vs. placebo -21.8%, p=0.003; -13.4%, p=0.06; and -16.3%, nominal p=0.03, respectively). Compared to the placebo group (9.4%), more patients achieved IGA 0/1 with cendakimab (720 mg once weekly: 33.3%, nominal p=0.004; 720 mg every 2 weeks: 24.4%, nominal p=0.06; 360 mg every 2 weeks: 38.2%, nominal p<0.001). Furthermore, more patients achieved EASI-75 with cendakimab than with placebo (720 mg once weekly: 50.0%, nominal p=0.02; 720 mg every 2 weeks: 48.2%, nominal p=0.03; 360 mg every 2 weeks: 52.7%, nominal p=0.01; placebo: 26.3%). Most reported AEs were mild or moderate [37].
Eblasakimab is a first-in-class mAb that prevents IL-4 and IL-13 signaling by binding to the IL-13Rα1 subunit. In the TREK-AD study, a Phase IIb DBPC trial, the efficacy and safety of eblasakimab were investigated in adult patients with moderate-to-severe AE. By week 16, eblasakimab at doses of 600 mg every 4 weeks, 300 mg every 2 weeks, and 400 mg every 2 weeks provided a greater reduction in EASI score: -73.0% (p=0.001), -69.8% (p=0.005), and -65.8% (p=0.029), respectively, compared to -51.1% with placebo. Additionally, the 600 mg every 4 weeks dose was significantly superior to placebo in achieving EASI-75 (52.0% vs. 24.4%, p=0.004) and EASI-90 (27.6% vs. 7.9%, p=0.008) at week 16. Eblasakimab administered every 2 weeks also showed significant improvements versus placebo: for 400 mg, EASI-75 and EASI-90 were 43.6% (p=0.036) and 25.3% (p=0.018), and for 300 mg, 51.0% (p=0.005) and 30.8% (p=0.003), respectively. Patients receiving eblasakimab reported a higher incidence of conjunctivitis (5.2% vs. 1.8%) and injection site reactions (4.7% vs. 1.8%) compared to placebo [38].

Anti-IL-31R
Nemolizumab is an antagonist of the IL-31 receptor alpha subunit, which induces pruritus and skin inflammation in AE. It has shown clinically significant efficacy in patients with moderate-to-severe AE accompanied by significant pruritus. In the 48-week Phase III DBPC trials ARCADIA1 and ARCADIA2, the drug led to statistically significant improvement: at week 16 in ARCADIA1, 36% of patients in the nemolizumab group achieved IGA success versus 25% in the placebo group (p=0.0003), and in ARCADIA2, 38% vs. 26% (p=0.0006). EASI-75 skin improvement was recorded in 44% of patients in ARCADIA1 (vs. 29% with placebo; p<0.0001) and 42% in ARCADIA2 (vs. 30% with placebo; p=0.0006). Itch reduction occurred as early as the first week. The safety profile of nemolizumab was comparable to placebo [39]. These results led to FDA approval of nemolizumab for the treatment of AE in patients ≥12 years [40].

Anti-OX40/OX40L
The interaction between the immune checkpoint molecule OX40 and its ligand OX40L plays a key role in the proliferation and survival of effector T-cells and the formation of memory T-cells. Patients with AE have an increased number of OX40+ T-cells in lesional skin and elevated OX40 expression on circulating CD4+ T-cells, indicating the importance of this signaling pathway in disease pathogenesis [24].
Amlitelimab, a mAb blocking OX40L, was studied in a Phase IIb DBPC trial. All doses of the drug showed a statistically significant reduction in EASI score compared to placebo (p<0.001). At week 24, patients with a positive response to therapy were split into groups continuing treatment or switching to placebo. By week 52, 71.9% of patients continuing treatment maintained an IGA score of 0/1, and 69.0% achieved EASI-75. In the group switched to placebo, the clinical effect was also maintained: IGA 0/1 in 57.0% and EASI-75 in 61.6%. The study confirmed not only the high efficacy of amlitelimab but also its prolonged action after discontinuation. AEs were observed with equal frequency across all groups [41].
Rocatinlimab, a mAb targeting the OX40 receptor, was evaluated in a Phase IIb DBPC trial. Compared to placebo (-15.0; 95% CI -28.6 to -1.4), a significant reduction in EASI score at week 16 was observed in all rocatinlimab groups (150 mg every 4 weeks: -48.3 [95% CI -62.2 to -34.0; p=0.0003]; 600 mg every 4 weeks: -49.7 [95% CI -64.3 to -35.2; p=0.0002]; 300 mg every 2 weeks: -61.1 [95% CI -75.2 to -47.0; p<0.0001]; 600 mg every 2 weeks: -57.4 [95% CI -71.3 to -43.4; p<0.0001]). The most pronounced clinical effect was recorded in the group receiving 300 mg every 2 weeks, where 54% of patients achieved EASI-75 (vs. 11% with placebo) and 37% achieved EASI-90 (vs. 4% with placebo). AEs were reported with similar frequency across all groups [42].
Telazorlimab is another anti-OX40 mAb investigated in a Phase IIb MRDBPCT. By week 16 of treatment, the mean reduction in EASI score was significantly greater in patients receiving telazorlimab 300 mg every 2 weeks (-54.4% vs. -34.2% with placebo, p=0.008) and 600 mg every 2 weeks (-59.0% vs. -41.8% with placebo, p=0.008). Patients receiving telazorlimab 300 mg every 2 weeks showed greater improvement compared to the placebo group, including a higher percentage achieving EASI-75 at week 16 (23.7% vs. 11.3%) and a greater frequency of IGA response (score 0/1 with a ≥2-point reduction from baseline) – 13.2% vs. 5.0%. The incidence of AEs was similar between patients receiving telazorlimab and placebo [43].

Allergic Rhinitis

Although to date no biologic, including omalizumab, is officially approved by the FDA for the treatment of allergic rhinitis (AR), it is the only mAb recommended by international position papers for patients with severe forms of AR [44].
Dupilumab was studied in patients with asthma and perennial AR. Those receiving dupilumab 300 mg every 2 weeks showed a statistically significant reduction in the Sino-Nasal Outcome Test (SNOT-22) score, with a decrease of 5.98 points (95% CI: -10.45 to -1.51; p=0.009). Furthermore, all key allergic rhinitis symptoms significantly improved: nasal congestion decreased by 0.60 points (95% CI: -0.96 to -0.25; p<0.01), rhinorrhea by 0.67 points (95% CI: -1.04 to -0.31; p<0.01), sneezing by 0.55 points (95% CI: -0.89 to -0.21; p<0.01), and postnasal drip by 0.49 points (95% CI: -0.83 to -0.16; p<0.01). The incidence of AEs was similar across all groups [45].
Stapokibart inhibits the interaction of IL-4R with both IL-4 and IL-13. A Phase III MRDBPCT involved patients with moderate-to-severe seasonal AR. Compared to placebo, stapokibart led to a significant reduction in nasal symptoms assessed by the reflective Total Nasal Symptom Score (rTNSS) over both 2 weeks (-1.3; 95% CI: -2.0 to -0.6; p=0.0008) and 4 weeks (-1.7; 95% CI: -2.5 to -0.8; p=0.0002). Treatment-emergent AEs were comparable between the two groups [46].

Eosinophilic Esophagitis

Although many mAbs have been studied for the treatment of eosinophilic esophagitis (EoE), they have demonstrated only histological improvements without significantly impacting dysphagia symptoms [47].
Cendakimab, a mAb targeting IL-13, a key cytokine involved in EoE pathogenesis, demonstrated clinical efficacy in a Phase III MRDBPCT in patients ≥12 years with EoE. By week 24 of treatment, a statistically significant proportion of participants receiving cendakimab achieved a histological response (reduction in esophageal eosinophil count to ≤6 cells per high-power field) – 28.6% vs. 2.2% in the placebo group (difference 26.4%; 95% CI 20.6 to 32.2; p<0.0001). Additionally, the number of days with dysphagia was significantly reduced compared to placebo (-6.1 vs. -4.2 days; difference -1.9; 95% CI -3.0 to -0.8; p=0.0005). By week 48 of treatment, patients who continued cendakimab weekly or switched to every two weeks maintained a statistically significant histological and clinical response. The number of AEs was comparable across all groups [48].

Food Allergy

Until recently, the only therapy for IgE-mediated food allergy (FA) was strict avoidance of culprit foods. However, for patients with polyvalent FA, adhering to an elimination diet is challenging. Oral immunotherapy (OIT) aims to induce clinical tolerance, although it is associated with a high rate of AEs [49].
Omalizumab, when used in combination with OIT, significantly enhances the latter's efficacy in patients with IgE-mediated FA, according to clinical trial results. A Phase II DBPC trial included children aged 4 to 15 years with confirmed polyvalent FA. Participants received omalizumab or placebo for the first 16 weeks, with OIT initiated at week 8 and continued for 28 weeks. Omalizumab use was significantly associated with a higher percentage of tolerance to 2 grams of protein from ≥2 causative foods (83% vs. 33%; OR: 10.0; 95% CI: 1.8-58.3; p=0.004) [50].
The OUtMATCH study was a Phase III MRDBPCT evaluating the efficacy and safety of omalizumab monotherapy for patients with multiple FAs. It involved patients aged 1 to 17 years with allergy to peanut and at least two other foods. Sixteen weeks of omalizumab treatment was more effective than placebo in increasing the threshold of reactivity to peanut protein to ≥600 mg (67% vs. 7%, p<0.001), and to tree nut, milk, and egg protein to ≥1000 mg (41% vs. 3%; 66% vs. 10%; 67% vs. 0%, respectively; p<0.001 for all comparisons) [51]. The results of this study formed the basis for the FDA's approval of omalizumab in 2024 for monotherapy of IgE-mediated FA [52].
Etokimab, a mAb blocking IL-33, was evaluated in a Phase IIa MRDBPCT in adult patients with confirmed peanut allergy. A single injection allowed 73% and 57% of patients to tolerate a cumulative dose of 275 mg of peanut protein by days 15 and 45, respectively, while this figure was 0% in the placebo group. Furthermore, a significant increase in the tolerated dose from baseline to day 15 was observed with etokimab (from 175 mg to 275 mg, p=0.001) but not with placebo (from 25 mg to 75 mg, p=0.63). Fewer AEs were observed in the etokimab group compared to the placebo group [53].

Chronic Spontaneous Urticaria

Complete control of chronic spontaneous urticaria (CSU) is achieved with H1-antihistamines in less than 10% of patients. Approximately 70% of CSU patients refractory to antihistamines also fail to achieve complete control with omalizumab [54], necessitating the investigation of other biologics.
Dupilumab demonstrated efficacy in the Phase III DBPC trials LIBERTY-CSU CUPID A and C compared to placebo in patients ≥6 years old, previously naïve to omalizumab. Pooled results from these two studies demonstrated a statistically significant reduction compared to placebo in weekly Itch Severity Score (ISS7): -9.9 vs. -6.7 (difference -3.2; p<0.0001) and weekly Urticaria Activity Score (UAS7): -19.3 vs. -13.1 (difference -6.2; p<0.0001). Furthermore, a significantly greater proportion of patients receiving dupilumab achieved well-controlled (UAS7≤6; 43.1% vs. 23.4%; OR 3.0; p<0.0001) or completely controlled (UAS7=0; 30.6% vs. 15.9%; OR 2.8; p<0.0001) disease compared to placebo [55]. Based on these results, in April 2025, the FDA expanded the indications for dupilumab to include CSU in patients ≥12 years [56].
Barzolvolimab is a mAb that binds to the stem cell factor receptor, blocking its interaction with its ligand, leading to suppression of mast cell activation and depletion of the mast cell pool. In a Phase II DBPC trial, barzolvolimab at doses of 150 mg every 4 weeks and 300 mg every 8 weeks showed a statistically significant improvement in the total UAS7 score at 12 weeks compared to placebo (-23.02/-10.47 [difference -12.55, p<0.0001] and -23.87/-10.47 [difference -13.41, p<0.0001], respectively). No serious AEs were reported [57].

Conclusion

Biologic therapy has revolutionized the treatment of severe allergic diseases by targeting key pathogenic pathways and offering effective solutions for patients with symptoms refractory to conventional therapy. Continued research into the pathophysiology of ADs is paramount for developing next-generation treatments. These advances pave the way for more effective, safer, and personalized approaches, ultimately improving the quality of life for patients with ADs. However, challenges remain regarding the registration of innovative mAbs in the Russian Federation, their accessibility, and long-term safety. Further high-quality research and appropriate administrative regulation are necessary for the successful integration of these new therapeutic approaches into routine clinical practice.