Delgocitinib

12.1 Mechanism of Action Delgocitinib, a Janus kinase (JAK) inhibitor, inhibits the activity of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). JAK signaling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, and activation and subsequent localization of STATs to the nucleus, leading to the expression of cytokine-responsive genes to induce specific biological responses in target cells. The exact mechanism of action of delgocitinib in the treatment of moderate to severe CHE is currently not known.

1 INDICATIONS AND USAGE ANZUPGO is indicated for the topical treatment of moderate to severe chronic hand eczema (CHE) in adults who have had an inadequate response to, or for whom topical corticosteroids are not advisable. ANZUPGO is a Janus kinase (JAK) inhibitor indicated for the topical treatment of moderate to severe chronic hand eczema (CHE) in adults who have had an inadequate response to, or for whom topical corticosteroids are not advisable. ( 1 ) Limitations of Use: Use of ANZUPGO in combination with other JAK inhibitors or potent immunosuppressants is not recommended. ( 1 ) Limitations of Use Use of ANZUPGO in combination with other JAK inhibitors or potent immunosuppressants is not recommended.

2 DOSAGE AND ADMINISTRATION See the full prescribing information for recommended immunizations prior to treatment. ( 2.1 ) Do not use more than 30 grams per 2 weeks or 60 grams per month. Apply twice daily to skin of the affected areas only on the hands and wrists. ( 2.2 ) For topical use only. Not for oral, ophthalmic, or intravaginal use. ( 2.2 ) 2.1 Recommended Immunizations Prior to Treatment Initiation Complete any necessary immunizations, including herpes zoster vaccinations, according to current immunization guidelines prior to ANZUPGO treatment [see Warnings and Precautions (5.3) ]. 2.2 Recommended Dosage and Administration Do not use more than 30 grams per 2 weeks or 60 grams per month. Prior to applying ANZUPGO, clean and dry affected areas. Apply a thin layer of ANZUPGO, twice daily, to the affected areas only on the hands and wrists. ANZUPGO is for topical use only. Not for oral, ophthalmic, or intravaginal use. Avoid contact with eyes, mouth, or other mucous membranes. If contact with mucous membranes occurs, rinse thoroughly with water.

6 ADVERSE REACTIONS Adverse reactions that were reported in ≤ 1% of subjects were application site pain, paresthesia, pruritus, erythema, and bacterial skin infections including finger cellulitis, paronychia, other skin infections, leukopenia, and neutropenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LEO Pharma Inc. at 1-877-494-4536 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of ANZUPGO was evaluated in two randomized, double-blind, multicenter, vehicle-controlled clinical trials (TRIAL 1 and TRIAL 2), in which 959 adults with moderate to severe CHE received ANZUPGO or vehicle cream topically twice daily for 16 weeks. A total of 638 subjects were treated with ANZUPGO [see Clinical Studies (14) ] . In TRIAL 1 and TRIAL 2, adverse reactions that were reported in ≤ 1% of subjects in the ANZUPGO group were application site pain, paresthesia, pruritus, erythema, and bacterial skin infections including finger cellulitis, paronychia, other skin infections, leukopenia, and neutropenia. In an open label extension trial (TRIAL 3), 801 subjects were treated for up to an additional 36 weeks after completing TRIAL 1 or TRIAL 2. A total of 198 subjects received continuous treatment with ANZUPGO for 52 weeks. Eczema herpeticum was observed in one subject and herpes zoster was observed in two subjects treated with ANZUPGO.