Delgocitinib (ANZUPGO) — TrialistMD Drug Profile

JAK Inhibitor · Dermatology · Chronic Hand Eczema · Topical

Delgocitinib

ANZUPGO® · LEO Pharma Inc.

A pan-JAK inhibitor (JAK1, JAK2, JAK3, TYK2) formulated as a 2% topical cream — the first topical JAK inhibitor approved by the FDA for chronic hand eczema. Indicated for moderate to severe CHE in adults with an inadequate response to, or for whom topical corticosteroids are not advisable, based on two pivotal Phase 3 trials (TRIAL 1 and TRIAL 2).

NDA Number 216660

Application Type NDA / Standard

Approval Date July 2025

Dosage Form Cream 2% (20 mg/g)

Route Topical

Sponsor LEO Pharma Inc.

Warnings & Precautions — Key Safety Signals

Serious Infections: May increase infection risk including eczema herpeticum and herpes zoster. Avoid use in active/serious infections.
Non-melanoma Skin Cancers: Basal cell carcinoma reported. Periodic skin examinations recommended; avoid sunlamps and excessive sun exposure.
Immunizations: Avoid live vaccines immediately before, during, and after treatment.
Potential JAK Inhibition Risks: Based on oral JAK inhibitor data in RA: ↑ all-cause mortality, MACE, thrombosis, malignancies vs TNF blockers. ANZUPGO not approved for RA. Lipid increases (TC, LDL, TG) observed with oral and topical JAK inhibitors.

Drug Overview

NDA 216660

Indication

Moderate–Severe CHE

Adults inadequate to TCS or TCS not advisable

Dose

BID Topical

Max 30 g / 2 weeks · 60 g / month

Pivotal Trials (N)

959

TRIAL 1 (n=487) · TRIAL 2 (n=472)

JAK Targets

Pan-JAK

JAK1, JAK2, JAK3, TYK2

Key Drug Information

Parameter	Detail
Proprietary Name	ANZUPGO® — LEO Pharma A/S registered trademark
INN / Generic Name	Delgocitinib
Drug Class	Janus kinase (JAK) inhibitor — pan-JAK (JAK1, JAK2, JAK3, TYK2)
Chemical Name	3-[(3S,4R)-3-Methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octan-1-yl]-3-oxopropanenitrile
Molecular Formula / MW	C₁₆H₁₈N₆O · 310.35 g/mol
Dosage Form	White to slightly brown cream; 2% (20 mg/g)
Route of Administration	Topical (hands and wrists only)
Manufacturer	LEO Laboratories Ltd., 285 Cashel Road, Dublin 12, Ireland
Distributor	LEO Pharma Inc., Madison, NJ 07940, USA
NDC	50222-280-30 (30 g tube) · 50222-280-60 (60 g tube)
Storage	20°C–25°C; excursions 15°C–30°C; do not freeze
PI Revision Date	July 2025

Mechanism of Action

Pan-JAK inhibition: Delgocitinib inhibits JAK1, JAK2, JAK3, and TYK2. JAK signaling involves recruitment of STATs to cytokine receptors, with subsequent STAT activation and nuclear localization, leading to cytokine-responsive gene expression. The exact mechanism in CHE is currently unknown.

Dosage & Administration

Parameter	Detail
Dose	Apply a thin layer twice daily to affected areas on the hands and wrists
Maximum Quantity	30 g per 2 weeks · 60 g per month
Application Site	Hands and wrists only; clean and dry prior to application
Restrictions	Not for oral, ophthalmic, or intravaginal use; avoid eyes, mouth, mucous membranes
Combination Limits	Not recommended with other JAK inhibitors or potent immunosuppressants
Pre-treatment	Complete immunizations including herpes zoster vaccines per current guidelines

Competitive Landscape — Topical CHE

Drug	Class	Route	Approval	Population
Crisaborole (EUCRISA)	PDE4 Inhibitor	Topical	Dec 2016	Adults & pediatric ≥3 months (AD)
Ruxolitinib (OPZELURA)	JAK1/2 Inhibitor	Topical	Sep 2021	Adults & adolescents ≥12 years (AD)
Delgocitinib (ANZUPGO)	Pan-JAK Inhibitor	Topical	July 2025	Adults (moderate–severe CHE)

AD = atopic dermatitis; CHE = chronic hand eczema. Competitive agents shown are approved topical agents with JAK or related mechanisms. Sources: FDA prescribing information and NDA 216660 medical review.

Baseline Characteristics

TRIAL 1 · TRIAL 2 · Combined N=959

Study population: Adults with moderate to severe CHE (IGA-CHE score 3 or 4) and a HESD itch score (weekly average) ≥4, who had a history of inadequate response to topical corticosteroids or for whom TCS were not advisable. Subjects were randomized to ANZUPGO or vehicle cream twice daily for 16 weeks.

Mean Age

44.1 yrs

Across all treatment arms (Trials 1 & 2)

Female

64%

of enrolled subjects

Age ≥65 years

59 of 691 exposed subjects

Severe CHE (IGA=4)

28%

Baseline IGA-CHE score of 4

Demographics by Treatment Arm

Pooled TRIAL 1 + TRIAL 2

Demographics

ANZUPGO Vehicle

Subjects (N) 638 321

Mean age (years) 44.1 44.1

Age ≥65 years 8% 8%

Female 64% 64%

White 90% 90%

Asian 4% 4%

Black 1% 1%

Hispanic / Latino 3% 3%

Baseline Disease Severity

ANZUPGO Vehicle

IGA-CHE = 3 (moderate) 72% 72%

IGA-CHE = 4 (severe) 28% 28%

Mean HESD itch score 7.1 7.1

Mean HESD pain score 6.7 6.7

HESD itch baseline ≥4 ~95% ~95%

HESD pain baseline ≥4 ~79% ~79%

CHE Subtype Distribution

Primary classification · Combined Trials

Primary CHE subtype — % of enrolled subjects

Atopic hand eczema

35.9%

Hyperkeratotic eczema

21.5%

Irritant contact dermatitis

19.6%

Allergic contact dermatitis

13.9%

Vesicular hand eczema

9.1%

Contact urticaria / PCD

0.1%

28% of subjects were diagnosed with two or more overlapping CHE subtypes. PCD = protein contact dermatitis.

Trial-Level Enrollment Summary

TRIAL 1 · TRIAL 2

Parameter	TRIAL 1 — ANZUPGO (N=325)	TRIAL 1 — Vehicle (N=162)	TRIAL 2 — ANZUPGO (N=313)	TRIAL 2 — Vehicle (N=159)
NCT ID	NCT04871711		NCT04872101
Total randomized	487		472
IGA-CHE TS responders (Wk 16)	20% (64/325)	10% (16/162)	29% (91/313)	7% (11/159)
HESD itch ≥4-pt improve (Wk 16)	47% (152/323)	23% (37/161)	47% (146/309)	20% (31/156)
HESD pain ≥4-pt improve (Wk 16)	49% (143/291)	28% (41/149)	49% (143/294)	23% (32/141)

Extension Trial (TRIAL 3)

NCT04949841 · Long-term safety cohort

Parameter	Detail
Enrolled from TRIAL 1 / 2 completers	801 subjects treated for up to an additional 36 weeks
Continuous delgocitinib exposure	198 subjects received uninterrupted treatment for 52 weeks
Eczema herpeticum	1 subject (ANZUPGO group)
Herpes zoster	2 subjects (ANZUPGO group)

Baseline characteristics are presented as pooled across TRIAL 1 and TRIAL 2 (all randomized subjects). Source: ANZUPGO Prescribing Information, NDA 216660 (Ref ID: 5629364, revised 7/2025).

Clinical Efficacy

TRIAL 1 · TRIAL 2 · 16-Week Treatment Period

Primary Endpoint

IGA-CHE TS at Wk 16

Score 0 or 1 + ≥2-pt improvement from baseline

Trial Design

RCT, DB, Vehicle-Ctrl

16-week + open-label extension (TRIAL 3)

Total Randomized (N)

959

TRIAL 1: 487 · TRIAL 2: 472

Eligible Population

IGA-CHE 3–4

HESD itch weekly avg ≥4 at baseline

Primary Endpoint — IGA-CHE Treatment Success at Week 16

TRIAL 1 (NCT04871711) — IGA-CHE TS at Week 16

ANZUPGO (N=325)

20%

Vehicle (N=162)

10%

Difference from vehicle: 10% (95% CI: 4%, 16%)

TRIAL 2 (NCT04872101) — IGA-CHE TS at Week 16

ANZUPGO (N=313)

29%

Vehicle (N=159)

Difference from vehicle: 22% (95% CI: 16%, 29%)

Symptom Endpoints — HESD Itch & Pain

HESD ITCH ≥4-POINT IMPROVEMENT at Week 16

Based on subjects with baseline itch score ≥4

TRIAL 1 — Drug

47%

TRIAL 1 — Vehicle

23%

Δ from vehicle: 24% (16%, 33%)

TRIAL 2 — Drug

47%

TRIAL 2 — Vehicle

20%

Δ from vehicle: 27% (19%, 36%)

HESD PAIN ≥4-POINT IMPROVEMENT at Week 16

Based on subjects with baseline pain score ≥4

TRIAL 1 — Drug

49%

TRIAL 1 — Vehicle

28%

Δ from vehicle: 22% (12%, 31%)

TRIAL 2 — Drug

49%

TRIAL 2 — Vehicle

23%

Δ from vehicle: 26% (17%, 35%)

Efficacy Endpoints Summary

Endpoint	TRIAL 1 — ANZUPGO	TRIAL 1 — Vehicle	TRIAL 2 — ANZUPGO	TRIAL 2 — Vehicle
IGA-CHE TS (Week 16)	20% (64/325)	10% (16/162)	29% (91/313)	7% (11/159)
HESD itch ≥4-pt improvement	47% (152/323)	23% (37/161)	47% (146/309)	20% (31/156)
HESD pain ≥4-pt improvement	49% (143/291)	28% (41/149)	49% (143/294)	23% (32/141)

Efficacy Over Time — IGA-CHE TS

ANZUPGO — TRIAL 1 ANZUPGO — TRIAL 2 Vehicle (pooled avg)

Values approximated from FDA-approved prescribing information Figure 1 (NDA 216660, Ref ID 5629364). IGA-CHE TS = IGA-CHE score 0 or 1 with ≥2-point improvement from baseline. Data after rescue treatment or permanent discontinuation counted as non-response.

Safety Profile

TRIAL 1 · TRIAL 2 · N=638 ANZUPGO-treated

Exposed to ANZUPGO

638

16-week double-blind period

Extension Cohort (TRIAL 3)

801

Up to 36 additional weeks

52-week Continuous Exposure

198

subjects in TRIAL 3

Contraindications

None

No absolute contraindications listed

Adverse Reactions (≤1% of ANZUPGO subjects)

Application Site Reactions Pain, paresthesia, pruritus, erythema — reported at application site; frequency ≤1%

Bacterial Skin Infections Finger cellulitis, paronychia, other skin infections — frequency ≤1%

Hematologic Leukopenia and neutropenia observed — frequency ≤1%

Eczema Herpeticum 1 subject in TRIAL 3 (extension). Viral reactivation signal. Monitor for HSV reactivation during treatment.

Herpes Zoster 2 subjects in TRIAL 3. Consider interrupting ANZUPGO until episode resolves.

Non-melanoma Skin Cancer Basal cell carcinoma reported. Periodic skin examinations recommended for all patients.

Warnings & Precautions Detail

Warning	Key Details
Serious Infections (5.1)	Avoid in active/serious infections. Consider risks in patients with chronic/recurrent infection, TB exposure, history of opportunistic infections. Monitor for signs of infection. Interrupt for serious infections.
Viral Reactivation (5.1)	Herpes virus reactivation (including zoster) reported. Hepatitis B/C reactivation risk unknown — patients with active hepatitis B/C excluded from trials. Screen per clinical guidelines; ANZUPGO not recommended in active hepatitis B or C.
Non-melanoma Skin Cancers (5.2)	Basal cell carcinoma observed. Periodic skin exams recommended. Avoid sunlamps; use sun-protective clothing / broad-spectrum sunscreen.
Immunizations (5.3)	Complete all age-appropriate vaccinations (including herpes zoster) before starting. Avoid live vaccines immediately before, during, and after treatment.
JAK Inhibition Risks (5.4)	Unknown whether topical ANZUPGO carries same systemic risks as oral JAK inhibitors. Reference: oral JAK inhibitor postmarketing RA safety trial — ↑ all-cause mortality, MACE, thrombosis, DVT, PE, malignancies vs TNF blockers (patients ≥50 years with ≥1 CV risk factor). Lipid increases with oral and topical JAK inhibitors.

Use in Specific Populations

Population	Guidance
Pregnancy (8.1)	Insufficient human data. No adverse developmental effects in animal studies at doses 120× (rat) or 193× (rabbit) MRHD by AUC. Fetal weight decreases and skeletal variations at doses ≥512× MRHD in rats.
Lactation (8.2)	No data on presence in human milk. Present in rat milk after oral administration. Advise breastfeeding women to avoid contact with nipple/surrounding area after applying to hands/wrists.
Pediatric (8.4)	Safety and efficacy not established.
Geriatric (8.5)	8.5% of exposed subjects were ≥65 years (n=59); 1.4% were ≥75 years (n=10). No overall differences in safety or effectiveness vs younger adults.

Pharmacokinetics

Topical Application · CHE Subjects

Mean Cmax (Day 1)

1.53 ng/mL

SD ±2.24; avg 0.87 g applied BID

AUC₀₋₁₂ (Day 1)

6.1 ng·h/mL

SD ±8.14; similar on Day 1 and Day 8

Half-life (t½)

~21 h

Estimated after repeated topical application

Plasma Protein Binding

22–29%

Low plasma protein binding

Plasma Conc (TRIAL 2)

0.35–0.50 ng/mL

Mean at Wks 1, 4, 16 (2–6 h post-dose)

Renal Excretion

~75%

Unchanged drug in urine (oral data)

Metabolism & Drug Interactions

Parameter	Detail
Accumulation	No evidence of accumulation with twice daily topical dosing
Main plasma component	Unchanged delgocitinib; does not undergo extensive metabolism
Metabolites	4 metabolites via oxidation and glucuronide conjugation; each <2% of unchanged drug
Primary CYP	CYP3A4/5 (primary); CYP1A1, CYP2C9, CYP2C19, CYP2D6 (minor)
CYP Inhibition / Induction	Does not inhibit or induce CYP enzymes at clinically relevant concentrations
Transporter Inhibition	Does not inhibit P-gp, BCRP, OATP, OAT, OCT, or MATE at clinically relevant concentrations
Clinical DDI Studies	Not conducted with ANZUPGO; topical route limits systemic exposure

Cardiac Electrophysiology

At 193 times the mean maximal plasma concentration from the recommended topical dose, clinically significant QTc interval prolongation was not observed.

Nonclinical Toxicology

Study	Finding
Dermal carcinogenicity (mouse, 2 yr)	Not carcinogenic at up to 5% ointment (~600× MRHD by AUC)
Oral carcinogenicity (rat, 2 yr)	Benign thymoma in female rats at 30 mg/kg/day (2274× MRHD); no neoplastic findings in males at same dose
Mutagenicity / Genotoxicity	Not mutagenic (Ames test); not clastogenic (in vivo rat bone marrow, human lymphocytes)
Male fertility (rat)	No impairment at up to 30 mg/kg/day (1308× MRHD)
Female fertility (rat)	Decreased fertility index & corpora lutea, increased implantation loss at 100 mg/kg/day (5897× MRHD); no adverse effects at 30 mg/kg/day (1087× MRHD)

Regulatory Overview

NDA 216660 · LEO Pharma Inc.

NDA Type

NDA / 505(b)(1)

Standard review pathway

Approval

July 2025

First topical JAK inhibitor for CHE

Indication (approved)