Roflumilast Cream (ARQ-151)

Roflumilast cream (ARQ-151) is being investigated for the treatment of psoriasis and atopic dermatitis.

  • Roflumilast cream is uniquely formulated as an emollient, water-based (~50% water) cream without fragrances, propylene glycol, isopropyl alcohol, or ethanol
  • Importantly, roflumilast cream contains an exclusive emulsifier designed to maintain epidermal intercellular lipids and is adjusted to a stratum corneum pH, at which the skin normally functions
  • Roflumilast cream is being investigated to address unmet needs, including as potential long-term topical therapy that can be used on all areas of the body

Roflumilast Cream (ARQ-151) in Psoriasis

Landscape

  • High-potency steroids are limited to short-term use1
  • Steroid-sensitive areas, such as the face, neck, and intertriginous areas can be challenging to treat and require additional considerations1
  • Patient adherence to existing topical therapies is generally low and influenced by dissatisfaction or frustration with onset of efficacy, fear of adverse effects, and inconvenience or messiness1-3
  • Patients with psoriasis experience quality-of-life deficits, reduced work productivity, and sleep disturbances4,5

Mechanism

  • Phosphodiesterase 4 (PDE4) activity is elevated in psoriatic skin6
  • Inhibition of PDE4 reduces proinflammatory factors and restores the skin barrier4
  • Roflumilast cream (ARQ-151) is a selective, highly potent PDE4 inhibitor that is being investigated as a treatment for psoriasis
Skin with psoriasis.

Clinical Program Results

Phase 1/2a study results are published in the Journal of Drugs in Dermatology.7

Phase 2b study results are published in the New England Journal of Medicine.8

Infographic showing eligibility, 12 week dosing period, and endpoints.

aIGA success and I-IGA success were defined as scores of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline.
BSA, body surface area; IGA, Investigator's Global Assessment; I-IGA, Intertriginous IGA; PASI, Psoriasis Area and Severity Index; PASI 75, 75% reduction in PASI score; PASI 90, 90% reduction in PASI score; QD, once daily; WI-NRS, Worst Itch Numeric Rating Scale.

Infographic of phase 2 study results.

aThe first time point after the start of roflumilast treatment was week 2.
CI, confidence interval; IGA, Investigator’s Global Assessment; I-IGA, Intertriginous Investigator’s Global Assessment; TEAE, treatment-emergent adverse event.

Additional data from the phase 2b study of roflumilast cream in patients with plaque psoriasis were presented at the 29th European Academy of Dermatology and Venerology Congress.

A phase 2 long-term study of patients with plaque psoriasis (NCT03764475) demonstrated durability of response through 52 weeks and similar safety

Two phase 3 studies (DERMIS-1/-2) have been completed (NCT04211363 and NCT04211389)9

Infographic showing eligibility, 8 week dosing, and endpoints of phase 3 study.

aIGA success and I-IGA success were defined as scores of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline.
BSA, body surface area; IGA, Investigator's Global Assessment; I-IGA, Intertriginous Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PASI 50, 50% reduction in PASI score; PASI 75, 75% reduction in PASI score; QD, once daily; WI-NRS, Worst Itch Numeric Rating Scale.

Infographic showing roflumilast meeting primary endpoint of statistically significant achievement of IGA success at week 8.

aIGA success and I-IGA success were defined as scores of 0 or 1 (clear or almost clear) with at least a two-grade improvement from baseline.
AE, adverse event; IGA, Investigator's Global Assessment; I-IGA, Intertriginous Investigator's Global Assessment; SAE, serious adverse event; TEAE, treatment-emergent adverse event.
Lebwohl et al. Presented at the European Academy of Dermatology and Venereology Spring Symposium 2021; May 6-7, 2021; Virtual.

Roflumilast Cream (ARQ-151) in Atopic Dermatitis

Landscape

  • Atopic dermatitis is a common, chronic inflammatory skin disease affecting both children and adults10
  • Itch is the most burdensome symptom, causing patients to experience substantially reduced quality of life and sleep disturbances11
  • The skin barrier is typically compromised in atopic dermatitis12
  • Topical corticosteroids and emollients are the standard of care12
  • Steroids are not suitable for long-term use, and children are at risk of greater systemic absorption12

Mechanism

  • Elevated PDE4 levels are found in the keratinocytes of individuals with atopic dermatitis12
  • Inhibition of PDE4 decreases inflammatory response and pruritus12,13
  • Roflumilast cream (ARQ-151) is a selective, highly potent PDE4 inhibitor being investigated as a treatment for atopic dermatitis
Skin with atopic dematitis.

Clinical Program Results

Phase 2 study has been completed (NCT03916081)13

Infographic showing eligibility, 4 weeks dosing, and endpoints of phase 2 study.

BSA, body surface area; EASI, Eczema Area And Severity Index; QD, once daily; WI-NRS, Worst Itch Numeric Rating Scale.

Study data from the phase 2b study of roflumilast cream in patients with atopic dermatitis were presented at EADV 2020.

Infographic of study data from phase 2b study of roflumilast cream in patients with atopic dermatitis.

  • Treatment-emergent adverse events (TEAEs) and local tolerability of irritation and stinging and burning of roflumilast cream were similar to vehicle14
  • All TEAEs were mild or moderate, with low rates of application site AEs14
Data presented for intent-to-treat population. AE, adverse event; CI, confidence interval; EASI, Eczema Area and Severity Index; LS, least squares; TEAE, treatment-emergent adverse event; vIGA-AD, Validated Investigator Global Assessment for Atopic Dermatitis.

Two phase 3 studies (INTEGUMENT-1/-2) have been initiated for roflumilast cream in atopic dermatitis (NCT04773587); (NCT04773600)15

Infographic showing eligibility, 4 week dosing, and endpoints of phase 3 studies.

aIGA success was defined as a score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline.
EASI-75, Eczema Area and Severity Index 75% improvement; IGA, Investigator's Global Assessment; QD, once daily; vIGA-AD, Validated Investigator's Global Assessment for Atopic Dermatitis; WI-NRS, Worst Itch Numeric Rating Scale.

A phase 3 trial in pediatric patients aged 2-5 years is ongoing (INTEGUMENT-PED: NCT04845620)

A phase 3 long-term study is ongoing (INTEGUMENT-OLE: NCT04804605)

References

1. Torsekar and Gautam. Indian Dermatol Online J. 2017;8:235-245. 2. Brown et al. J Am Acad Dermatol. 2006;55:607-613. 3. van de Kerkhof et al. J Eur Acad Dermatol Venereol. 2015;29:2002-2010. 4. Bhosle et al. Health Qual Life Outcomes. 2006;4:35. 5. Henry et al. PLoS One. 2016;11:e0157843. 6. Li et al. Front Pharmacol. 2018;9:1048. 7. Papp et al. J Drugs Dermatol. 2020;19:734-740. 8. Lebwohl et al. N Engl J Med. 2020;383:229-239. 9. Lebwohl et al. Presented at the European Academy of Dermatology and Venereology Spring Symposium 2021; May 6-7, 2021; Virtual. 10. Bieber. Ann Dermatol. 2010;22:125-137. 11. Silverberg et al. Ann Allergy Asthma Immunol. 2018;121:340-347. 12. Nygaard et al. Dermatology. 2017;233:333-343. 13. Bäumer et al. Inflamm Allergy Drug Targets. 2007;6:17-26. 14. Gooderham et al. Presented at: 29th European Academy of Dermatology and Venereology Congress; October 29-31, 2020; Virtual. 15. Data on file, Arcutis Biotherapeutics.

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