Dr. Weidinger discussed the anti-Ox40-ligand antibody amlitelimab and how it performed in the phase 2b Stream-AD trial.

The anti-Ox40-ligand antibody amlitelimab performed well in the phase 2b Stream-AD trial of adults with moderate-to-severe atopic dermatitis, according to research presented at the European Academy of Dermatology and Venereology (EADV) Congress 2023 in Berlin.

Amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups studied (250 mg with 500 mg loading dose (LD), 250 mg without LD, 125 mg without LD, 62.5 mg without LD or placebo Q4W).

The 250 mg with LD group had the numerically highest response versus placebo at Week 16, the researchers found.

Patients treated with amlitelimab experienced up to 61.5% improvement in average Eczema Area and Severity Index (EASI) score from baseline at week 16, the primary endpoint, with continued improvement seen through 24 weeks, the study showed. What's more, clinically meaningful improvements were seen in all key secondary endpoints at week 16 with continued improvements through week 24, including for Investigator Global Assessment (IGA 0/1) where patients on the highest dose experienced 22.1% improvement at week 16 which increased to 45.5% by week 24. Amlitelimab was well-tolerated and no fever/chills, oral ulcers, or imbalances with conjunctivitis were observed across doses.

Study author Stephan Weidinger, MD, PhD, a professor of dermatology at the Christian-Albrechts-University and vice-head of the department of dermatology and Allergy at the University Hospital Schleswig-Holstein in Campus Kiel, Germany, spoke to DermWire about the findings and their implications,

 
Why is this topic important to study?

Stephan Weidinger, MD, PhD: "Atopic dermatitis is often associated with a significant psychosocial and quality of life impact on patients who suffer from symptoms like persistent itch and skin lesions. This can cause physical discomfort, emotional distress, embarrassment, social stigma, and daily activity limitation. While we have made significant strides in the treatment of this disease, there are still patients who do not respond or incompletely respond to existing treatments and continue to suffer from the burdensome symptoms. Also, deep, and durable responses appear to be difficult to achieve. There is a continued need for new treatment options."

What role do you see amlitelimab playing in AD?

Dr. Weidinger: "Amlitelimab by virtue of its mechanism targeting OX40-ligand, a central regulator of immune response, modulates both type 2 and non-type 2 inflammation.  Thus, amlitelimab targets a broader patient population than mechanisms targeting type 2 inflammation, and therefore may provide efficacy for patients who incompletely respond or do not respond to mechanisms targeting type 2 inflammation."

How is OX40-Ligand involved in AD?

Dr. Weidinger:  "OX40-Ligand and receptor interaction is a key step early in inflammation that can lead to disease. Inhibiting this interaction has the potential to block multiple pathways early in the inflammatory cascade."
 
What is the next step?

Dr. Weidinger:  "These data form the basis for advancement into Phase 3 clinical development in AD, which is expected to begin in the first half of 2024."
 

Why is it important to have new drugs in AD with new mechanisms of action?

Dr. Weidinger: "While we have made significant strides in the treatment of atopic dermatitis, there is much heterogeneity between patients and within patients over time, and there are patients who do not respond or incompletely respond to existing treatments and need alternative treatment options. As is the case with most chronic diseases, a one-size-fits-all approach to treatment is not achievable and patients and physicians require a diverse toolkit of options for treating these diseases. "