Atopic dermatitis improves with amlitelimab during, after treatment

Key takeaways:

• Significant improvement in IGA and EASI scores were found in patients treated with amlitelimab vs. placebo.
• Many maintained improvement through week 52 whether they continued or withdrew from the treatment.

Patients with moderate to severe atopic dermatitis treated with amlitelimab showed both clinical and biomarker improvements, including in patients who withdrew from treatment, according to phase 2b trial results.

A fully human, nondepleting, anti-OX40L immunoglobulin G4 monoclonal antibody, amlitelimab inhibits T-cell-dependent pathogenic inflammation.

“Unlike the conventional biologics that we now have available for atopic dermatitis, amlitelimab does not target one single cytokine or receptor, but rather it acts higher up in the immune cascade and restores homeostasis of those T cells that produce these cytokines and that are directly involved in the whole inflammatory response,” Stephan Weidinger, MD, PhD, director of the department of dermatology at the University Hospital Schleswig-Holstein and lead study author, told Healio.

The two-part, phase 2b, randomized, double-blinded, placebo-controlled, parallel-group, dose-ranging STREAM-AD trial included a 28-day screening and washout period, a 24-week treatment period in part 1 and a 28-week maintenance/withdraw period in part 2.

Patients were randomly assigned to one of five groups in part 1: amlitelimab 500 mg loading dose followed by 250 mg, amlitelimab 250 mg, amlitelimab 125 mg, amlitelimab 62.5 mg or placebo. With the exception of the loading dose, all patients received their doses every 4 weeks through week 20.

In part 2, patients who achieved IGA 0/1 or EASI 75 in part 1 were again randomly assigned to receive placebo (withdraw), or to continue their part 1 dose through week 48.

At week 24, those in the loading dose plus 250 mg treatment group achieved a –64.4% least-squares mean change from EASI baseline; the 250 mg group had a –52.2% change, the 125 mg group had a –53.7% change, the 62.5 mg group had a –54.4% change and the placebo group had a –27.6% change.

IGA 0/1 was achieved by 45.5%, 33.3%, 40.3%, 29.1% and 11.4% of the five respective groups, whereas EASI 75 was achieved by 54.5%, 38.5%, 49.4%, 40.5% and 17.7%.

Additionally, Peak Pruritus Numerical Rating Scale score reductions of at least four points were recorded in 31.2%, 24.4%, 28.6%, 27.8% and 7.6% of patients at week 24.

Of those who continued their amlitelimab treatment regimen, 71.9% maintained IGA 0/1 and 69% maintained EASI 75 through week 52. For those who were assigned to withdraw from the drug, IGA 0/1 was maintained by 57% and EASI 75 by 61.6%.

Serum amlitelimab concentrations also remained constant through both study parts for those who continued treatment, whereas it reduced over time in those assigned to placebo in part 2.

Serum biomarker levels including Th2-related IL-13, IL-31 and TARC and TH17/Th22-related IL-17A and IL-22 were reduced in all patients treated with amlitelimab, as were serum LDH, total IgE and blood eosinophil levels.

“We have seen in STREAM-AD that multiple proinflammatory markers including non-type-2 cytokines as well as eosinophils which are not reduced by existing biologics showed prolonged decreases, which differentiates amlitelimab from other drugs, from a biomarker perspective,” Weidinger said. “The clinical implications are that this may be a biologic treatment for long-term management of patients with moderate to severe AD that can modulate the exaggerated T-cell responses and lead to long-lasting and durable disease control.”

Treatment-emergent adverse events occurred in 69.8% of those who continued amlitelimab in part 2 and 71.9% of those who withdrew, as well as 66.7% of those in the placebo groups of both parts. The most common treatment-emergent adverse events in the pooled amlitelimab groups were headache and upper respiratory tract infection.

A phase 3 clinical trial program for amlitelimab is currently underway studying the drug as monotherapy as well as in combination with topical steroids.

“There is a new biologic at advanced stages of clinical development that offers a different mode of action as compared to the existing ones that clinically may lead to efficacy across the very heterogeneous patient population,” Weidinger said.

For more information:

Stephan Weidinger, MD, PhD, can be reached at sweidinger@dermatology.uni-kiel.de.