Biologics for atopic dermatitis, 'four-way race'

First IL-31 inhibitor to join…administration convenience offers strength in convenience

Follow-up results continue to emerge…development of various interleukin inhibitors is accelerating

The biologic market for atopic dermatitis is experiencing a new shift. Competition among interleukin (IL)-13 inhibitors has been previously centered around 'Dupixent.' As treatments with new mechanisms enter the race, multi-layer competition is intensifying, with drugs that differ in their immune pathways. 

(clockwise from left) Nemluvio, Dupixent, Adtralza, Ebglyss

According to industry sources on the 4th, Galderma Korea has recently received domestic approval for its biologic agent 'Nemluvio (nemolizumab).' The indication is for the treatment of moderate-to-severe atopic dermatitis and prurigo nodularis (PN). 

With the addition of Nemluvio to the previously approved treatments, including Sanofi and Regeneron's Dupixent (dupilumab), LEO Pharma's Adtralza (tralokinumab), and Eli Lilly's Ebglyss (lebrikizumab)—the therapeutic options in the Korean atopic dermatitis market have expanded to four.

Nemluvio is the only IL-31 receptor inhibitor among the drugs approved in Korea, targeting a distinctly different immune axis compared to existing treatments that inhibit the Th2 axis related to IL-13.

IL-31 is a neuro-immune cytokine that induces itch signals, sitting at the center of a vicious cycle in which it directly stimulates sensory nerves, exacerbating scratching behavior.

Unlike existing drugs like Dupixent (IL-4/13) and Adtralza or Ebglyss (IL-13), which focus on inflammation control, Nemluvio's mechanistic differentiation lies in its direct blockage of itching, the core symptom of the disease burden.

In clinical trials, Nemluvio, when combined with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI), met all endpoints compared with placebo.

Notably, the speed of itch improvement is rapid. In the global Phase 3 ARCADIA study, Nemluvio showed a statistically significant reduction in itching compared to placebo starting from 48 hours after administration, and at the 4-week and 16-week marks, more than twice as many patients compared to the placebo group experienced a clinically meaningful level of itch relief (PP-NRS improvement of 4 points or more).

Regarding inflammation and lesion improvement, the Eczema Area and Severity Index 75% improvement (EASI-75) was 43.5% and 42.1% in ARCADIA-1 and ARCADIA-2, respectively, indicating a level of inflammation suppression similar to that of existing Th2 inhibitors.

Administration convenience is also a strength. For atopic dermatitis, Nemluvio is administered at an initial dose of 60mg followed by 4-week intervals up to 16 weeks, and it is the only drug in Korea that can be switched to an 8-week dosing interval once a clinical response is confirmed.

Considering that Dupixent and Ebglyss are both administered every 2 weeks, and Adtralza is administered every 2 or 4 weeks, Nemluvio is the first drug to provide a dosing interval optimization model based on clinical response.

Analysis suggests that, given the essential role of long-term treatment for moderate-to-severe patients, this can significantly enhance market competitiveness by improving patient convenience and compliance.

Clinical safety also showed no significant difference compared to existing treatments. Adverse events reported relatively frequently with existing biologics, such as conjunctivitis and herpes, showed no significant difference between the Nemluvio and placebo groups, and most adverse events were manageable at mild to moderate levels.

New target competition intensifies… IL-22·IL-18 inhibitors are being developed

As atopic dermatitis is recognized as a multi-immune network disease that is difficult to explain by the inhibition of a single cytokine, new drug development is rapidly shifting from a Th2-centric approach to a multi-mechanism competition targeting various immune axes, such as IL-31, IL-22, and IL-18.

Among these, the IL-22 inhibitor 'temtokibart,' being developed by LEO Pharma, is considered one of the most notable next-generation candidates.

IL-22 is a key cytokine that induces epidermal proliferation, decreased barrier function, and chronic inflammation. IL-22 inhibition offers a distinct approach to existing Th2 inhibitors by simultaneously promoting skin barrier recovery and relieving inflammation.

Temtokibart binds to IL-22RA1 (IL-22 receptor α1) to block IL-22 signaling and has the potential to inhibit the IL-20 and IL-24 pathways that share the same receptor. Thus, its strength lies in its upstream signal-inhibition mechanism, which regulates the entire epidermal barrier function and inflammatory pathways rather than blocking a single cytokine.

In a Phase 2a study, temtokibart achieved EASI-90 in 30.8% of patients and EASI-100 in 20.9%, with broad reductions in systemic inflammatory proteins.

Additionally, temtokibart was evaluated as the first mechanistic candidate to directly regulate epidermis-immune interactions, as it was shown to simultaneously inhibit the Th17/22, Th2, and Th1 axes and restore the expression of barrier genes such as KRT and CLDN.

Another new drug candidate, camoteskimab from the U.S. biotech company Apollo Therapeutics, showed an 80% improvement in EASI scores in Phase 2a and maintained clinical responses even in the patient group that failed Dupixent.

Since IL-18 is known as an upstream regulator of Th1, Th2, Th17, and Th22, it is expected to be a meaningful alternative for patients who did not respond to existing treatments. Korean company AprilBio and the U.S. drug development company Evommune have also entered Phase 2 clinical trials with this same mechanism.