Opzelura Drug Information

Recommended Dosage and

Administration for Atopic Dermatitis OPZELURA is for topical use only. OPZELURA is not for ophthalmic, oral, or intravaginal use. Instruct patients to apply a thin layer of OPZELURA twice daily to affected areas of up to 20% body surface area.

Do not use OPZELURA with occlusive dressings. Stop using when signs and symptoms (e.g., itch, rash, and redness) of atopic dermatitis resolve. If signs and symptoms do not improve within 8 weeks, patients should be re-examined by their healthcare provider . Adult and Pediatric Patients 12 Years of Age and Older Do not use more than one 60 gram tube of OPZELURA per week or one 100 gram tube per 2 weeks.

Pediatric Patients 2 to 11 Years of Age Do not use more than one 60 gram tube of OPZELURA per 2 weeks.

Recommended Dosage and

Administration for Nonsegmental Vitiligo OPZELURA is for topical use only. OPZELURA is not for ophthalmic, oral, or intravaginal use. Instruct patients to apply a thin layer of OPZELURA twice daily to affected areas of up to 10% body surface area.

Do not use more than one 60 gram tube of OPZELURA per week or one 100 gram tube per 2 weeks. Satisfactory patient response may require treatment with OPZELURA for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be re‑evaluated by the healthcare provider .

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 practice. Adverse Reactions in Adult and Pediatric Subjects 2 Years of Age and Older with Atopic Dermatitis Adult and Pediatric Subjects 12 Years of Age and Older In two double-blind, vehicle-controlled clinical trials (TRuE-AD1 and TRuE-AD2), 499 adult and pediatric subjects 12 years of age and older with atopic dermatitis were treated topically with OPZELURA twice daily for 8 weeks . The adverse reactions reported by ≥ 1% of OPZELURA treated subjects and at a greater incidence than in the vehicle arm are listed in Table 1. Table 1: Adverse Reactions Occurring in ≥ 1% of Adult and Pediatric Subjects 12 Years of Age and Older Treated with OPZELURA for Atopic Dermatitis through Week 8 in TRuE-AD1 and TRuE-AD2 Adverse Reaction OPZELURA (N = 499) n (%) Vehicle (N = 250) n (%) Nasopharyngitis 13 2 Bronchitis 4 0 Ear infection 4 0 Eosinophil count increased 4 0 Urticaria 4 0 Diarrhea 3 1 (< 1) Folliculitis 3 0 Tonsillitis 3 0 Rhinorrhea 3 1 (< 1) Adverse reactions that occurred in TRuE-AD1 and TRuE-AD2 in < 1% of subjects in the OPZELURA group and none in the vehicle group were: neutropenia, allergic conjunctivitis, pyrexia, seasonal allergy, herpes zoster, otitis externa, Staphylococcal infection, and acneiform dermatitis. No clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects 12 to 17 years of age.

Pediatric Subjects 2 to 11 Years of Age In a double-blind, vehicle-controlled clinical trial (TRuE-AD3), 130 pediatric subjects 2 to 11 years of age with mild to moderate atopic dermatitis were treated topically with OPZELURA twice daily for 8 weeks . The adverse reactions reported by ≥ 1% of subjects treated with OPZELURA and at a greater incidence than in the vehicle arm are listed in Table 2. Table 2: Adverse Reactions Occurring in ≥ 1% Pediatric Subjects 2 to 11 Years of Age Treated with OPZELURA for Atopic Dermatitis through Week 8 in TRuE-AD3 Adverse Reaction OPZELURA (N = 130) n (%) Vehicle (N = 65) n (%) Upper respiratory tract infection Upper respiratory tract infection includes upper respiratory tract infection, nasopharyngitis, rhinorrhea, oropharyngeal pain, respiratory tract congestion, viral upper respiratory tract infection 20 7 COVID-19 6 2 Application site reaction Application site reaction includes application site pain, application site irritation, application site discomfort, application site pruritus 6 1 Pyrexia 3 0 White blood cell decreased White blood cell decreased includes white blood cell decreased, leukopenia 2 0 Subjects with cytopenias (defined as hemoglobin < 10 g/dL, absolute neutrophil count (ANC) < 1000/μL, and platelet count < 100,000/μL) at screening were excluded from the trial. The impact of OPZELURA on blood cell counts in this population has not been studied. Adverse Reactions in Adult and Pediatric Subjects 12 Years of Age and Older with Nonsegmental Vitiligo In two double-blind, vehicle-controlled clinical trials (TRuE-V1 and TRuE-V2), 449 adult and pediatric subjects 12 years of age and older with nonsegmental vitiligo were treated topically with OPZELURA twice daily for 24 weeks . The adverse reactions reported by OPZELURA treated subjects with an incidence of ≥ 1% and at least 1% greater incidence than in the vehicle arm in the 24-week double-blind period are listed in Table 3. Table 3: Adverse Reactions Occurring in ≥ 1% of Adult and Pediatric Subjects 12 Years of Age and Older Treated with OPZELURA for Nonsegmental Vitiligo through Week 24 in TRuE-V1 and TRuE-V2 Adverse Reaction OPZELURA (N = 449) n (%) Vehicle (N = 224) n (%) Application site acne 26 2 Application site pruritus 23 6 Nasopharyngitis 19 5 Headache 17 6 Urinary tract infection 7 1 (< 1) Application site erythema 7 1 (< 1) Pyrexia 6 0 Adverse reactions that occurred in TRuE-V1 and TRuE-V2 in ≥ 0.5% to < 1% of subjects in the OPZELURA group and none in the vehicle group were: application site dermatitis, hypertension, anxiety, application site discoloration, application site folliculitis, dermatitis contact, diarrhea, ear infection, gastritis, gastroenteritis, hordeolum, influenza-like illness, insomnia, nasal congestion, and vomiting.

No clinically meaningful differences in safety or effectiveness were observed between adults and pediatric subjects.

Drug interaction studies with OPZELURA have not been conducted. Ruxolitinib is known to be a substrate for cytochrome P450 3A4 (CYP3A4). Inhibitors of CYP3A4 may increase ruxolitinib systemic concentrations whereas inducers of CYP3A4 may decrease ruxolitinib systemic concentrations . Strong Inhibitors of CYP3A4 Avoid concomitant use of OPZELURA with strong inhibitors of CYP3A4 as there is a potential to increase the systemic exposure of ruxolitinib and could increase the risk of OPZELURA adverse reactions .

Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463 or visiting www.opzelura.pregnancy.incyte.com. Risk Summary Available data from pregnancies reported in clinical trials with OPZELURA are not sufficient to evaluate a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

In animal reproduction studies, oral administration of ruxolitinib to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses associated with maternal toxicity (see Data). The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risk in the U.S. general population of major birth defects and miscarriage is 2-4% and 15-20%, respectively.

Data Animal Data Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. There were no treatment-related malformations at any dose. A decrease in fetal weight of approximately 9% was noted in rats at the highest and maternally toxic dose of 60 mg/kg/day.

This dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (MRHD; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitis-affected body surface area is used for calculation of multiples of human exposure). In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 70% the MRHD clinical systemic exposure. In a pre-and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day.

There were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the MRHD clinical systemic exposure).

Pediatric Use Atopic Dermatitis The safety and effectiveness of OPZELURA for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis have been established in non-immunocompromised pediatric patients ages 2 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Use of OPZELURA in this age group is supported by evidence from adequate and well-controlled trials in adults and pediatric subjects ages 2 years and older with mild to moderate atopic dermatitis. Trials included 92 subjects 12 to 17 years of age and 130 subjects 2 to 11 years of age treated with OPZELURA. Application site reactions, pyrexia, and decreased white blood cell were reported more frequently in pediatric subjects ages 2 to ll years compared to adults and pediatric subjects ages 12 years and older . The safety and effectiveness of OPZELURA have not been established in pediatric patients younger than 2 years of age with atopic dermatitis.

Nonsegmental Vitiligo The safety and effectiveness of OPZELURA for the topical treatment of nonsegmental vitiligo have been established in pediatric patients ages 12 years and older. Use of OPZELURA in this age group is supported by evidence from TRuE-V1 and TRuE-V2, which included 55 subjects ages 12 to 17 years with nonsegmental vitiligo . The safety and effectiveness of OPZELURA have not been established in pediatric patients younger than 12 years of age with nonsegmental vitiligo. Juvenile Animal Toxicity Data Oral administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures.

When administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures occurred at doses ≥ 5 mg/kg/day. When administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. Males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period.

These findings were observed at systemic exposures that are at least 45% the MRHD in pediatric subjects 2 to 11 years of age (the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 35-50% atopic dermatitis-affected body surface area in pediatric subjects 2 to 11 years of age is used for the calculation of multiples of human exposure in this subsection).