JAK1 inhibitor cream (ARQ-252)

Overview

Janus kinase 1 (JAK1) inhibitor cream (ARQ-252) is being investigated for the treatment of chronic hand eczema and vitiligo.

ARQ-252 is a selective, highly potent,^* topical JAK1 inhibitor that demonstrates greater in vitro potency for JAK1 than JAK2.¹

*In vitro data. Clinical efficacy claims cannot be made.

Chronic hand eczema

Topical JAK1 inhibitor cream (ARQ-252) in chronic hand eczema.

Clinical landscape

Chronic hand eczema is a form of eczema that is located on the hands and/or wrists. Symptoms may include itching, burning, crusting, and scaling²
Chronic hand eczema may negatively affect quality of life, and incurs a substantial economic burden (eg, reduced work productivity)^3,4
A considerable unmet need exists for new therapies for hand eczema since few therapies are approved⁴

Proposed MOA

Inhibition of JAK has been shown to reduce pruritus in vitro⁵
ARQ-252 is a selective, highly potent,^* topical, small-molecule JAK1 inhibitor that is being investigated for the treatment of chronic hand eczema¹

*In vitro data. Clinical efficacy claims cannot be made.

MOA = mechanism of action

Clinical programs

Phase 1/2

A phase 1/2b study of ARQ-252 in chronic hand eczema has been completed.

ClinicalTrials.gov identifier: NCT04378569

Summary of results

The primary endpoint was not met, with none of the ARQ-252 cohorts achieving statistical significance vs vehicle

Reformulation is underway to improve local drug delivery to the skin

View Study Details

Vitiligo

Topical JAK1 inhibitor cream (ARQ-252) in vitiligo.

Clinical landscape

Vitiligo is an autoimmune condition characterized by the appearance of white macules on the skin as a result of the selective loss of melanocytes⁶
There are limited approved therapies to treat vitiligo
Physician-recommended therapies include narrow-band ultraviolet B, tacrolimus, and topical steroids⁷

Proposed MOA

Repigmentation of the skin has been demonstrated in some patients with vitiligo following inhibition of the JAK signal transducer and activator of transcription (STAT) pathway⁸
ARQ-252 is a selective, highly potent,^* topical, small-molecule JAK1 inhibitor that is being investigated for the treatment of vitiligo¹

*In vitro data. Clinical efficacy claims cannot be made.

MOA = mechanism of action

Clinical programs

Phase 2

A phase 2a trial of topical JAK inhibitor cream in nonsegmental facial vitiligo has been terminated.

ClinicalTrials.gov identifier: NCT04811131

Summary of results

Decision to terminate was based on analyses of the formulation used in both this vitiligo study and the recently completed phase 2b chronic hand eczema study
Analyses of the chronic hand eczema study pointed toward inadequate local drug delivery to the skin as a key driver of the lack of efficacy
The vitiligo study was not terminated for safety or tolerability reasons
Reformulation is underway to improve local drug delivery to the skin

View Study Details

References

1. Data on File. Arcutis Biotherapeutics, Inc. 2. Agner and Elsner. JEADV. 2020;34(Suppl. 1):4-12. 3. Bingefors et al. Acta Derm Venereol. 2011;91:452-458. 4. Dibenedetti et al. J Clin Aesthet Dermatol. 2015;8:19-27. 5. Howell et al. Front Immunol. 2019;10:2342. 6. Bergqvist and Ezzedine. Dermatology. 2020;236:571-592. 7. Ezzedine et al. Lancet. 2015;386:74-84. 8. Liu et al. J Am Acad Dermatol. 2017;77:675-682.