OX40-OX40L Inhibition for the Treatment of Atopic Dermatitis—Focus on Rocatinlimab and Amlitelimab

Abstract

Despite the recent emergence of targeted therapeutic options, there are still unmet needs concerning moderate-to-severe atopic dermatitis treatment. This review aims to discuss the OX40-OX40L pathway as a therapeutic target for the treatment of atopic dermatitis. OX40 and OX40L are two checkpoint molecules that bind to potentiate pro-inflammatory T-cell responses that are pivotal to atopic dermatitis pathogenesis. Two OX40-OX40L inhibitors, rocatinlimab and amlitelimab, are being developed for the treatment of atopic dermatitis. Rocatinlimab, an anti-OX40 antibody, was evaluated in phase 2b, a randomized, placebo-controlled clinical trial. At week 16, rocatinlimab groups achieved a greater reduction in the EASI percentage change from the baseline (−48.3% to −61.1%) against the placebo (−15.0%; p < 0.001), and clinical response was maintained 20 weeks after the treatment had ceased. Amlitelimab, an anti-OX40L antibody, was studied in a 12-week treatment phase 2a clinical trial, with a significant efficacy response observed within 2 weeks. At week 16, amlitelimab groups reached the EASI mean percentage change from the baseline of −69.9% and −80.1% versus the placebo (−49.4%; p = 0.072 and p = 0.009). Among the responders, 68% of amlitelimab patients were sustained 24 weeks following the last dose. Both treatments were shown to be safe and well tolerated. Current evidence points to OX40-OX40L inhibitors as future options for atopic dermatitis treatment with potential disease-modifying effects.

The Efficacy and Effectiveness of the Biological Treatment of Pruritus in the Course of Atopic Dermatitis

“…IL-25 and TSLP increase the expression of OX40L on dendritic cells, inducing the differentiation of OX40-positive T cells. Interleukin 33 stimulates the expression of OX40L on dendritic cells and type two innate lymphoid cells [ 77 , 78 ].…”

“…Amlitelimab is a human IgG4-class monoclonal antibody targeting OX40L. It binds to the ligand, blocking its reaction with the OX40 receptor, but causes no reduction in OX40 + T cells [ 77 , 79 ].…”

“…Additionally, a significant decrease in IL-22 serum level was reported after 16 weeks. No such correlation was observed in the placebo group [ 77 ]. Four further clinical studies on amlitelimab in atopic dermatitis are currently registered [ 55 ].…”

Type 2 inflammation and biological therapies in asthma: Targeted medicine taking flight

“…Amlitelimab is a human mAb that binds to the OX40-ligand (OX40L) and offers a potential novel treatment for asthma. OX40L is expressed on antigen-presenting cells, such as DCs, endothelial cells, macrophages, and activated B cells ( Lé and Torres, 2022 ; Sanofi, 2022 ). OX40 is expressed on regulator and effector T cells.…”

New molecules for atopic dermatitis treatment beyond biological therapy

“…As already mentioned, advances in knowledge regarding the pathophysiology of AD have allowed the development of new pharmacological options. Several biologic drugs are under investigation for AD: lebrikizumab (anti-IL-13), nemolizumab (anti-IL-31R) rocatinlimab, and amlitelimab (both anti-OX40) (Table 1) [25][26][27]. Ivarmacitinib (SHR0302) is a novel selective JAK1 inhibitor (Table 1).…”