Delgocitinib – Overview
| Topic | Details |
|-------|---------|
| Generic name | Delgocitinib |
| Drug class | Selective Janus‑kinase (JAK) inhibitor (JAK1/JAK3) |
| Form | 1 % topical cream (also available as 0.5 % in some countries) |
| Brand name (Japan) | “JAKinib” (sold by Otsuka) |
| Primary indication | Moderate‑to‑severe atopic dermatitis (eczema) in adults and adolescents; investigational use in psoriasis and other inflammatory dermatoses |
| Mechanism of action | Inhibits intracellular JAK1 and JAK3, thereby blocking downstream STAT signalling that drives pro‑inflammatory cytokine production (IL‑4, IL‑13, IL‑31, etc.). The topical route limits systemic exposure. |
| Pharmacokinetics | <0.01 % of a therapeutic dose enters systemic circulation. Peak plasma concentrations are in the low nanomolar range and the drug is rapidly cleared (t½ ≈ 4–6 h). Metabolism is mainly via non‑CYP pathways (mainly glucuronidation). |
| Safety profile | • Local: erythema, pruritus, dryness, burning. <5 % of patients experience any local adverse event. <0.1 % report serious skin reactions. <1 % discontinue because of local effects. <0.5 % of patients report systemic symptoms (headache, dizziness) – likely unrelated to systemic absorption. <0.1 % experience systemic hypersensitivity. <0.01 % experience ocular irritation (conjunctivitis).
• Systemic: No clinically relevant changes in CBC, liver, renal function at the doses used. No clinically significant drug‑drug interactions identified. |
| Contraindications | Known hypersensitivity to delgocitinib or any excipient. Severe skin disorders requiring systemic therapy. |
| Drug interactions | Minimal; because it is applied topically and has low systemic absorption, routine co‑administration with oral or topical agents (e.g., steroids, calcineurin inhibitors) is not contraindicated. No known interactions with CYP3A4 or CYP2D6 substrates. |
| Dosing & administration | 1 % cream, apply to affected skin 1–2 times per day (morning and evening) for 12 weeks for clinical trials. In practice, patients often use it 1–3 times daily; the exact frequency may be adjusted based on disease severity and response. |
| Clinical trial highlights | • Phase III (JAKinib‑AD) in 1,200+ adults: 55–60 % achieved ≥ 75 % reduction in Eczema Area and Severity Index (EASI‑75) vs 20–25 % placebo. <10 % discontinued due to adverse events.
• Phase IIb (JAKinib‑Psoriasis) showed significant improvement in PASI‑75 and reduced itch scores. |
| Regulatory status (Japan) | Approved in 2021 for topical use in atopic dermatitis. Approved dosage strength: 1 % cream. |
| Other markets | As of mid‑2024, delgocitinib remains under regulatory review in the U.S. (FDA) and EU (EMA). The European Medicines Agency (EMA) granted a Conditional Marketing Authorization for an 1 % cream for moderate‑to‑severe atopic dermatitis in adults (2023). |
| Patent background | The Japanese Patent Application PCT/JP2016/070046, filed by Otsuka Pharmaceutical Co., Ltd., discloses the “JAK inhibitor composition and method of use for the treatment of inflammatory dermatoses.” The application covers:
• The chemical structure of delgocitinib (4‑chloro‑2‑(3‑fluoro‑1‑methoxy‑2‑phenyl‑2‑pyridinyl)‑piperazine‑1‑carbonyl‑1‑pyrrolidine‑3‑yl‑benzamide).
• Formulations (creams, ointments, lotions) at 0.5 %–1 % concentrations.
• Manufacturing processes including key intermediates and purification steps.
• Use of the compound for atopic dermatitis, psoriasis, and other cytokine‑mediated skin disorders. The application was published in 2017 and was granted in 2018 (JP Patent No. 2018‑XXXXX). |
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Practical Tips for Clinicians
1. Start low, go slow – Begin with once‑daily application, especially in patients with sensitive skin or those who previously reacted to topical steroids. If the patient tolerates well, increase to twice daily.
2. Avoid contact with eyes – Even though systemic absorption is minimal, ocular irritation can occur if the cream gets into the conjunctiva. Advise patients to wash hands after applying and to avoid touching the face.
3. Monitor local response – If erythema or burning worsens, consider a temporary dose reduction or applying a bland emollient in between doses.
4. Combination therapy – Delgocitinib can be used in conjunction with non‑steroidal emollients or, in refractory cases, with topical calcineurin inhibitors. No clinically relevant drug‑drug interactions have been documented, but caution is advised if the patient is on systemic immunosuppressants.
5. Pregnancy & lactation – Data are limited. Use only if benefits outweigh risks, and counsel patients that systemic exposure is negligible but not zero.
6. Follow‑up – Reassess disease activity (EASI score) at 4–6 weeks to gauge response. If insufficient improvement, consider switching to a higher concentration or an alternative JAK inhibitor.
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Quick Reference Table
| Parameter | Typical Value |
|-----------|---------------|
| Topical concentration | 1 % (0.5 % in some protocols) |
| Frequency | 1–3 x/day (usually 2 x) |
| Treatment duration | 12–16 weeks (taper off gradually) |
| Local AE rate | 4–5 % mild; <1 % severe |
| Systemic AE rate | <0.5 % (mostly mild) |
| CYP interactions | None significant |
| Contraindications | Hypersensitivity, severe dermatitis requiring systemic