Topical AMTX-100 Proves Safe, Effective for Atopic Dermatitis in Phase 1 Trial

Yashar Salek

Credit: LinkedIn

A potential topical therapy that targets novel pathways of atopic dermatitis has advanced in clinical assessment after promising safety, tolerability and efficacy outcomes in a phase 1 trial.¹

In data presented at the Revolutionizing Atopic Dermatitis (RAD) 2023 Spring Conference in Washington, DC, this weekend, a team of investigators supported by Amytrx Therapeutics showed that investigative topical AMTX-100 CF 1.1% was associated with no dose-limiting toxicities nor treatment-related adverse events (AEs) while providing decreased body surface area (BSA) to treated patients with mild to moderate atopic dermatitis.

The findings supported the progression of the would-be agent to phase 2 trials, while investigators praised its unique properties in potentially mitigating atopic dermatitis.

Led by Yashar Salek, senior director of clinical development and acting director of safety and pharmacovigilance at Amarex Clinical Research, investigators sought to define maximum-tolerated dosage, as well as safety, tolerability and efficacy outcomes with topical AMTX-100 CF 1.1% in adults with mild to moderate atopic dermatitis.

While atopic dermatitis pathogenesis is generally linked to type 2 immune responses including elevated Th2 cytokine expression in the interleukin (IL) 4, 5, 13 and 31 pathways, previous research has highlighted the significance of IL-25, IL-33 and thymic stromal lymphopoietin—signifying epithelial cell-derived cytokine involvement—as well as IL-17, IL-22, and IL-23—signifying type 3 immune responses—in disease progression.

“Given that atopic dermatitis is a heterogeneous disease with potential for the activation of multiple cytokines at once, there is a growing interest in multi-factorial approaches to therapeutic intervention,” Salek and colleagues wrote. “Evidence indicates that transcription of many genes overexpressed in atopic dermatitis are controlled predominantly by stress responsive transcription factors (SRTFs) like nuclear factor-kB (NF-kB), the master regulator of inflammation.”

AMTX-100, a novel, chimeric, 100% human, 28-amino acid peptide, features cell-penetrating sequences at its amino terminal end, as well as NF-kB amino acid sequences containing a nuclear location sequence involved with the transport of large transcription factors (SRTFs)—“a new and untapped key target with broad activity for treating inflammation,” the team noted.

In the open-label, dose-escalation trial, investigation team assessed a 1.1% topical dose of the agent, administered twice-daily for 7 days, at 5 different dose levels in 26 trial participants. Administered doses were based on patient BSA percentage due to atopic dermatitis. They sought a primary endpoint of maximum dose toxicity, and a safety endpoint of treatment-emergent AEs. Additional endpoints included percent change in BSA from baseline and validated Investigator Global Assessments (vIGA) at days 7 and 21 of treatment.

Eligible patients were ≥18 years old with mild to moderate atopic dermatitis diagnoses for ≥6 months prior to enrollment. Fourteen (53.8%) patients were male, and mean age was 48.7 years old. Patients reported a mean baseline BSA of 1.9; a majority of patients reported a vIGA score of 3 (57.7%), indicating moderate atopic dermatitis.

Investigators observed no instances of dose-limiting toxicities nor treatment-emergent AEs among treated patients. Relevant laboratory measurements remained consistent for patients as well.

What’s more, Salek and colleagues reported a mean BSA decrease of 37.5% at day 7 (P = .001) and 37.9% at day 21 (P = .027)—as well as improved vIGA scores for atopic dermatitis post-intervention.

“The findings for this phase I portion of an adaptive phase 1/2 protocol provides support for safety, tolerability, and efficacy of AMTX-100 CF 1.1% in adult patients with mild to moderate atopic dermatitis,” investigators concluded. “AMTX-100 CF 1.1% has advanced into phase 2 study including safety, efficacy, gene expression (skin and blood), and proteomics (blood) measurements throughout the study.”

References

1. ^{Salek Y, Dejman M, Baya A, Mekonnen H, et al. Patients with Mild to Moderate Atopic Dermatitis: A first-in-human, Open- label, Dose-escalating, Non-Randomized Clinical Trial with AMTX-100. Paper presented at: Revolutionizing Atopic Dermatitis 2023 Spring Conference; April 29 – May 1, 2023; Washington, DC. Accessed April 30, 2023.}