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ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from
Paul Changelian1, Canxin Xu1, Steve Mnich1
1Aclaris Therapeutics, Chesterbrook, Pennsylvania, USA.
JID Innovations : Skin Science From Molecules to Population Health
|February 1, 2024
Summary
A new topical treatment, ATI-1777, significantly reduced atopic dermatitis symptoms in adults. This potent Janus kinase (JAK) inhibitor showed promising efficacy with minimal systemic exposure and no serious side effects.
Area of Science:
- Dermatology
- Immunology
- Pharmacology
Background:
- Atopic dermatitis (AD) is a chronic, itchy skin condition affecting a significant portion of the population.
- Existing treatments aim to manage symptoms, but novel therapeutic approaches are needed.
- ATI-1777 is a potent and selective Janus kinase 1 and 3 (JAK1/3) inhibitor designed for topical application to maximize skin efficacy and minimize systemic exposure.
Purpose of the Study:
- To evaluate the preliminary clinical efficacy and safety of ATI-1777 topical solution in adult patients with moderate to severe atopic dermatitis.
- To assess the pharmacokinetic profile of ATI-1777 following topical application.
Main Methods:
- A Phase 2a, randomized, double-blind, vehicle-controlled study (ATI-1777-AD-201) was conducted in 48 adult participants with atopic dermatitis.
- Participants received either ATI-1777 topical solution or a vehicle control for 4 weeks.
- The primary endpoint was the change in a modified Eczema Area and Severity Index (EASI) score from baseline.
Main Results:
- ATI-1777 demonstrated a statistically significant greater reduction in modified EASI scores compared to vehicle on day 28 (74.45% vs. 41.43%, P < .001).
- Average plasma concentrations of ATI-1777 remained below 5% of the concentration required for half-maximal inhibition of JAK1/3.
- No deaths or serious adverse events were reported during the study.
Conclusions:
- Topical ATI-1777 effectively reduced clinical signs of atopic dermatitis in adults.
- The treatment exhibited a favorable safety profile with no significant systemic drug exposure.
- ATI-1777 represents a potential new therapeutic option for managing atopic dermatitis.
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