JAK1 Inhibitor ARQ-252 Cream

ARQ-252 is a selective, highly potent,1* topical Janus kinase 1 (JAK1) inhibitor being investigated as a cream for the treatment of chronic hand eczema and vitiligo.

  • ARQ-252 demonstrates greater potency* in vitro for JAK1 than JAK21
  • *In vitro data. Clinical efficacy claims cannot be made.

Topical JAK1 Inhibitor Cream (ARQ-252) in Chronic Hand Eczema

Landscape

  • Chronic hand eczema is a common condition that occurs in different forms,2 negatively affects 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

Mechanism

  • Inhibition of JAK has been shown to reduce pruritus in vitro5
  • ARQ-252 is a selective, highly potent,1* topical, small-molecule JAK1 inhibitor that is being investigated for the treatment of chronic hand eczema
  • *In vitro data. Clinical efficacy claims cannot be made.
Hand with eczema.

Development

  • A phase 1/2b study has been completed (NCT04378569)
  • 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

Topical JAK1 Inhibitor Cream (ARQ-252) in Vitiligo

Landscape

  • There are limited approved therapies to treat vitiligo
  • Physician-recommended therapies include narrow-band ultraviolet B, tacrolimus, and topical steroids6

Mechanism

  • Repigmentation of the skin has been demonstrated in some patients with vitiligo following inhibition of the JAK signal transducer and activator of transcription (STAT) pathway7
  • ARQ-252 is a selective, highly potent,1* topical, small-molecule JAK1 inhibitor that is being investigated for the treatment of vitiligo
  • *In vitro data. Clinical efficacy claims cannot be made.
Dark haired woman with vitiligo on her face.

Development

  • A phase 2a trial of topical JAK inhibitor cream in nonsegmental facial vitiligo has been terminated (NCT04811131)
  • Decision 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

References

1. Data on file, Arcutis Biotherapeutics. 2. Diepgen et al. Br J Dermatol. 2009;160:353-358. 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. Ezzedine et al. Lancet. 2015;386:74-84. 7. Liu et al. J Am Acad Dermatol. 2017;77:675-682.

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