Small wins for amlitelimab in STREAM-AD

The experimental drug amlitelimab has scored positive outcomes in the double-blind, placebo-controlled phase IIb STREAM-AD study evaluating it as a treatment for moderate-to-severe atopic dermatitis (AD).

Four doses of amlitelimab – a fully human nondepleting, noncytoxic anti-OX40 ligand monoclonal antibody – were tested and each was significantly better than placebo at reducing AD severity 24 weeks into the treatment. (EADV 2023, abstract 6744]

Amlitelimab 250 mg, with a loading dose of 500 mg, had the greatest change in Eczema Area and Severity Index (EASI) from baseline of –32.1 percent at week 16.

“Across all four doses studied, we saw consistent improvements in important signs and symptoms of the disease, with an unremarkable safety profile,” said study author Dr Stephan Weidinger from the Christian-Albrechts University and vice-head of the Department of Dermatology at the University Hospital Schleswig-Holstein, Germany. “The study provides more insights into the drug’s potential, and a signal, to pursue a differentiated dosing regimen that could be meaningful to patients with severe AD.”

Alternative AD therapies warranted

While significant strides have been made in the treatment of AD, there are patients with suboptimal responses to currently available therapies and may require alternative treatments. “These patients continue to suffer from symptoms, including persistent itch and skin lesions,” he added.

Novel targeting of OX40 ligand-expressing antigen-presenting cells with amlitelimab is a novel way to modulate persistent inflammation in AD.

In the current dose-ranging study, Weidenger and his team tested amlitelimab in 390 adults with moderate-to-severe AD not adequately controlled with topical medications or for whom topical medications are unsuitable.

The study was designed into two parts – a 24-week treatment period, and a 36-week maintenance/withdrawal period, which is currently ongoing. Results from the 24-week treatment period were presented at EADV 2023.

Patients were randomly assigned to one of four subcutaneous doses of amlitelimab (250 mg with a 500 mg loading dose, 250 mg without a loading dose, 125 mg without a loading dose, or 62.5 mg without a loading dose) every 4 weeks.

EASI, IGA scores better with amlitelimab

Reduction in EASI score from baseline was greatest in patients taking 250 mg with 500 mg loading dose (–32.1 percent, 95 percent confidence interval [CI], –43.9 to –20.3; p<0.0001)) followed by 62.5 mg (–30.2, 95 percent CI, –41.9 to –18.5; p<0.0001), 250 mg (–27.3, 95 percent CI, –39.1 to –15.6; p<0.0001), and 125 mg (–22.2, 95 percent CI, –34 to –10.4; p=0.0002).

There were also clinically meaningful improvements in all key secondary endpoints. Twenty-two percent and 45.5 percent of patients treated with amlitelimab 250 mg with loading dose achieved an Investigator’s Global Assessment Scale (IGA) score of 0/1 (0=clear, 1=almost clear) at weeks 16 and 24, respectively, compared with 5.1 percent and 11.4 percent in the placebo group (p=0.0022 and p<0.0001).

Of patients treated with the same dose, 40.3 percent and 54.5 percent achieved a 75-percent reduction from baseline in EASI (EASI-75) at weeks 16 and 24, respectively, compared with 11.4 percent and 17.7 percent with placebo (p<0.0001 for both).

Amlitelimab substantially reduced the levels of certain biomarkers elevated in AD, including Th2-related IL-13 and TARC, Th17/Th22-related IL-17A and IL-22, and blood eosinophil counts, across all doses at weeks 16 and 24, with significant reduction in the 250 mg with loading dose group as early as week 4.

The data add to the growing body of evidence that targeting OX40-ligand potentially stops the inflammatory cascade across multiple pathways, with significant benefits for patients.

By targeting OX40-ligand, amlitelimab aims to restore balance between pro-inflammatory and regulatory T cells. The findings also serve as a basis for amlitelimab to proceed to a phase III trial, which will commence in 2024.