Skyrizi Drug Information

Plaque Psoriasis SKYRIZI ® is indicated for the treatment of moderate-to-severe plaque psoriasis in adults and pediatric patients 6 years of age and older who are candidates for systemic therapy or phototherapy.

Psoriatic Arthritis SKYRIZI is indicated for the treatment of active psoriatic arthritis in adults and pediatric patients 6 years of age and older.

Crohn’s Disease SKYRIZI is indicated for the treatment of moderately to severely active Crohn's disease in adults.

Ulcerative Colitis SKYRIZI is indicated for the treatment of moderately to severely active ulcerative colitis in adults.

Procedures Prior to Treatment Initiation For the treatment of moderately to severely active Crohn’s disease and ulcerative colitis, obtain liver enzymes and bilirubin levels prior to initiating treatment with SKYRIZI. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI. Complete all age-appropriate vaccinations as recommended by current immunization guidelines.

General Considerations for Administration •

Visually inspect SKYRIZI for particulate matter and discoloration prior to administration. The solution may contain a few translucent to white particles. ○ SKYRIZI 55 mg/0.37 mL prefilled syringe, 150 mg/mL prefilled pen or prefilled syringe, 180 mg/1.2 mL prefilled syringe or prefilled cartridge, and 360 mg/2.4 mL prefilled cartridge: a colorless to yellow, and clear to slightly opalescent solution. ○ SKYRIZI 90 mg/mL prefilled syringe and 600 mg/10 mL vial: a colorless to slightly yellow, and clear to slightly opalescent solution. ○ Do not use if the solution contains large particles or is cloudy or discolored. • Discard after use. Table 1.

SKYRIZI may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs). Table 2. After proper training: Adults ○ Adults may self-inject SKYRIZI.

Pediatric Patients 6 Years of Age and Older ○ For pediatric patients 10 years of age and older, it is recommended that SKYRIZI be administered by or under the supervision of an adult. ○ For pediatric patients 6 to less than 10 years of age, SKYRIZI should be administered by an adult. Before injecting, remove the carton with SKYRIZI from the refrigerator and without removing the prefilled pen or prefilled syringe from the carton, allow SKYRIZI to reach room temperature out of direct sunlight (30 to 90 minutes for the prefilled pen and 15 to 30 minutes for the prefilled syringe). Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis.

Administration of SKYRIZI in the upper, outer arm may only be performed by a healthcare professional or caregiver. If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

The SKYRIZI “Instructions for Use” contains more detailed instructions on the preparation and administration of SKYRIZI. Instruct the patient to read the Instructions for Use before administration.

Recommended Dosage for Moderately to Severely Active Crohn’s Disease Adult Patients: Induction The recommended induction dosage of SKYRIZI is 600 mg administered by intravenous infusion over a period of at least one hour at Week 0, Week 4, and Week 8. Use the lowest effective dosage needed to maintain therapeutic response.

Recommended Dosage for Moderately to Severely Active Ulcerative Colitis Adult Patients: Induction The recommended induction dosage of SKYRIZI is 1,200 mg administered by intravenous infusion over a period of at least two hours at Week 0, Week 4, and Week 8.

Preparation and Administration Instructions ( Moderately to Severely Active Crohn’s Disease and Ulcerative Colitis) Intravenous Induction Dosing Regimen: 1. SKYRIZI vial for intravenous administration is intended for administration by a healthcare provider using aseptic technique. 2. Prior to intravenous administration, determine the dose and number of SKYRIZI vials needed based on the patient’s indication (see table below).

Discard any remaining solution in the vial. Table 3. Total Volume of Diluent Required for Intravenous Induction Dose 3.

Infuse the diluted solution intravenously over a period of at least one hour for the SKYRIZI 600 mg dose; at least two hours for the SKYRIZI 1,200 mg dose. If stored refrigerated, allow the diluted SKYRIZI solution in the infusion bag or glass bottle to warm to room temperature prior to the start of the intravenous infusion. 4. Do not administer SKYRIZI diluted solution concomitantly in the same intravenous line with other medicinal products.

Handling and Storage of the Vial and the Diluted Solution: Do not shake the vial or diluted solution in the infusion bag or glass bottle. Use the prepared infusion immediately. If not used immediately, store the diluted SKYRIZI solution refrigerated and protected from light for up to 20 hours between 36°F to 46°F (2°C to 8°C).

Immediately after preparation or removal from refrigeration, the diluted SKYRIZI solution can be stored at room temperature at up to 77°F (25°C) (protected from sunlight) for up to 8 hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within 8 hours after dilution in the infusion bag.

Exposure to indoor light is acceptable during room temperature storage and administration. Do not freeze. Subcutaneous Maintenance Dosing Regimen: Using the single-dose 180 mg or 360 mg prefilled cartridge with On-Body Injector: SKYRIZI is intended for use under the guidance and supervision of a healthcare professional.

Patients may self-inject SKYRIZI using the on-body injector with prefilled cartridge after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI. Before using the on-body injector with prefilled cartridge, remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (45 to 90 minutes) without removing the prefilled cartridge or on-body injector from the carton.

Use the on-body injector to administer SKYRIZI 180 mg/1.2 mL or SKYRIZI 360 mg/2.4 mL prefilled cartridge subcutaneously on thigh or abdomen. Start the injection within 5 minutes after inserting the prefilled cartridge into the On-Body Injector. Using the 90 mg/mL or 180 mg/1.2 mL prefilled syringe: • Administer each SKYRIZI 90 mg/mL or 180 mg/1.2 mL prefilled syringe subcutaneously. • Patients may self-inject SKYRIZI after training in subcutaneous injection technique.

Inject one prefilled syringe after the other in different anatomic locations (such as thighs or abdomen). ▪ SKYRIZI 180 mg/1.2 mL prefilled syringe: One 180 mg prefilled syringe is required. ○ 360 mg maintenance dose: ▪ SKYRIZI 90 mg/mL prefilled syringes: Four 90 mg prefilled syringes are required.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse drug reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adults with Plaque Psoriasis A total of 2234 subjects were treated with SKYRIZI in clinical development trials in plaque psoriasis. Of these, 1208 subjects with psoriasis were exposed to SKYRIZI for at least one year.

Data from placebo- and active-controlled trials were pooled to evaluate the safety of SKYRIZI for up to 16 weeks. In total, 1306 subjects were evaluated in the SKYRIZI 150 mg group. Table 4 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the SKYRIZI group than the placebo group during the 16-week controlled period of pooled clinical trials.

Table 4. Adverse Reactions Occurring in ≥ 1% of Adults with Plaque Psoriasis on SKYRIZI through Week 16 Adverse reactions that occurred in < 1% but > 0.1% of subjects in the SKYRIZI group and at a higher rate than in the placebo group through Week 16 were folliculitis and urticaria. The rates of serious infections for the SKYRIZI group and the placebo group were ≤0.4%.

Serious infections in the SKYRIZI group included cellulitis, osteomyelitis, sepsis, and herpes zoster. Safety T hrough Week 52 Through Week 52, no new adverse reactions were identified, and the rates of the adverse reactions were similar to those observed during the first 16 weeks of treatment. During this period, serious infections that led to trial discontinuation included pneumonia.

Plaque Psoriasis of the Scalp or Genital Area The overall safety profile observed in clinical trials of subjects with moderate-to-severe plaque psoriasis of the scalp or genital area treated with SKYRIZI is generally consistent with the safety profile observed in previous clinical trials of subjects with moderate-to-severe plaque psoriasis. Adverse Reactions in Pediatric Subjects 6 Years of Age and Older with Plaque Psoriasis The safety of SKYRIZI was evaluated in a four-part trial that included 137 pediatric subjects 6 years of age and older with moderate-to-severe plaque psoriasis. Overall, the safety profile observed in pediatric subjects 6 years of age and older treated with SKYRIZI for up to 52 weeks was consistent with the safety profile observed in adult subjects with moderate-to-severe plaque psoriasis.

Adverse Reactions in Adult Subjects with Psoriatic Arthritis The overall safety profile observed in adult subjects with psoriatic arthritis treated with SKYRIZI is generally consistent with the safety profile in adult subjects with plaque psoriasis. There were no serious hepatic events reported. The incidence of hypersensitivity reactions was higher in the SKYRIZI group (n=16, 2.3%) compared to the placebo group (n=9, 1.3%).

One case of anaphylaxis was reported in a subject who received SKYRIZI in the Phase 2 clinical trial. Adverse Reactions in Adult Subjects with Crohn’s Disease SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active Crohn’s disease in two randomized, double-blind, placebo-controlled induction trials (CD-1, CD-2) and a randomized, double-blind, placebo-controlled, dose-finding trial (CD-4; NCT02031276). Long-term safety up to 52 weeks was evaluated in subjects who responded to induction therapy in a randomized, double-blind, placebo-controlled maintenance trial (CD-3).

Adverse reactions reported in > 3% of subjects in induction trials and at a higher rate than placebo are shown in Table 5. Table 5. Table 6.

Lipid Elevations: Elevations in lipid parameters (total cholesterol and low-density lipoprotein cholesterol ) were first assessed at 4 weeks following initiation of SKYRIZI in the induction trials (CD-1, CD-2). Increases from baseline and increases relative to placebo were observed at Week 4 and remained stable to Week 12. Following SKYRIZI induction, mean total cholesterol increased by 9.4 mg/dL from baseline to a mean absolute value of 175.1 mg/dL at Week 12.

Similarly, mean LDL-C increased by 6.6 mg/dL from baseline to a mean absolute value of 92.6 mg/dL at Week 12. Adverse Reactions in Adult Subjects with Ulcerative Colitis SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction trial (UC-1) and a randomized, double-blind, placebo-controlled, dose-finding trial (UC-3). The adverse reaction reported in ≥3% subjects treated with SKYRIZI in the ulcerative colitis induction trials (UC-1 and UC-3) and at a higher rate than placebo was arthralgia (3% SKYRIZI vs 1% placebo).

Adverse reactions reported in ≥3% of subjects treated with SKYRIZI in the maintenance trial (UC-2) and at a higher rate than placebo are shown in Table 7. Table 7. Adverse Reactions Reported in ≥3% of Subjects with Ulcerative Colitis Treated with SKYRIZI a in Placebo-Controlled 52-Week Maintenance Trial (UC-2) Specific Adverse Reactions The rates of infections, serious infections, and lipid elevations in subjects with UC who received SKYRIZI compared to subjects who received placebo in the induction trials (UC-1 and UC-3) and maintenance trial (UC-2) were similar to the rates in subjects with CD who received SKYRIZI compared to subjects who received placebo in the induction trials (CD-1, CD-2, and CD-4) and maintenance trial (CD-3). 6. 2 Postmarketing Experience The following adverse reactions have been reported during post-approval of SKYRIZI.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to SKYRIZI exposure: Skin and subcutaneous tissue disorders: eczema and rash

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while treated with SKYRIZI. Patients should be encouraged to enroll by calling 1-877-302-2161 or visiting http://glowpregnancyregistry.com. Risk Summary Available pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.

Although there are no data on risankizumab-rzaa, monoclonal antibodies can be actively transported across the placenta, and SKYRIZI may cause immunosuppression in the in utero - exposed infant. There are adverse pregnancy outcomes in women with inflammatory bowel disease (see Clinical Considerations). In an enhanced pre- and post-natal developmental toxicity study, pregnant cynomolgus monkeys were administered subcutaneous doses of 5 or 50 mg/kg risankizumab-rzaa once weekly during the period of organogenesis up to parturition.

Increased fetal/infant loss was noted in pregnant monkeys at the 50 mg/kg dose (see Data). No risankizumab-rzaa-related effects on functional or immunological development were observed in infant monkeys from birth through 6 months of age. The clinical significance of these findings for humans is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth. Fetal/Neonatal adverse reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester.

Therefore, SKYRIZI may be present in infants exposed in utero. The potential clinical impact of risankizumab exposure in infants exposed in utero should be considered. Data Animal Data An enhanced pre- and post-natal developmental toxicity study was conducted in cynomolgus monkeys.

Pregnant cynomolgus monkeys were administered weekly subcutaneous doses of risankizumab-rzaa of 5 or 50 mg/kg from gestation day 20 to parturition, and the cynomolgus monkeys (mother and infants) were monitored for 6 months after delivery. No maternal toxicity was noted in this study. There were no treatment-related effects on growth and development, malformations, developmental immunotoxicology, or neurobehavioral development.

The increased fetal/infant loss in the 50 mg/kg group was considered to be related to risankizumab-rzaa treatment. The no-observed adverse effect level (NOAEL) for maternal toxicity was identified as 50 mg/kg, and the NOAEL for developmental toxicity was identified as 5 mg/kg. In the infants, mean serum concentrations increased in a dose-dependent manner and were approximately 17%-86% of the respective maternal concentrations.

Following delivery, most adult female cynomolgus monkeys and all infants from the risankizumab-rzaa-treated groups had measurable serum concentrations of risankizumab-rzaa up to 91 days postpartum. Serum concentrations were below detectable levels at 180 days postpartum.

Pediatric Use Moderate-to-Severe Plaque Psoriasis The safety and effectiveness of SKYRIZI for the treatment of moderate-to-severe plaque psoriasis have been established in pediatric patients 6 years of age and older who are candidates for systemic therapy or phototherapy. Use of SKYRIZI for this indication is supported by evidence from a four-part trial in a total of 137 pediatric subjects 6 years of age and older with moderate-to-severe plaque psoriasis. In addition to two lead-in pharmacokinetic cohorts, the trial also included a randomized, efficacy assessor-blinded, active treatment-controlled cohort that enrolled 82 pediatric subjects 12 years of age and older and a single-arm, open-label cohort that enrolled 30 pediatric subjects 6 to less than 12 years of age.

The safety and effectiveness of SKYRIZI have not been established in pediatric patients younger than 6 years of age with moderate-to-severe plaque psoriasis. Active Psoriatic Arthritis The safety and effectiveness of SKYRIZI for the treatment of psoriatic arthritis have been established in pediatric patients 6 years of age and older. Use of SKYRIZI for this indication is supported by evidence from well-controlled studies of SKYRIZI in adults with psoriatic arthritis, pharmacokinetic data from adult patients with psoriatic arthritis or plaque psoriasis, and pharmacokinetic, safety, and immunogenicity data from pediatric patients with moderate-to-severe plaque psoriasis.

Risankizumab exposures in pediatric patients with psoriatic arthritis at the recommended dosage are predicted to be comparable to those observed in adults with psoriatic arthritis based on population pharmacokinetic modeling and simulation. Crohn’s Disease and Ulcerative Colitis The safety and effectiveness of SKYRIZI have not been established in pediatric patients with Crohn’s disease or ulcerative colitis.

SKYRIZI is contraindicated in patients with a history of serious hypersensitivity reaction to risankizumab-rzaa or any of the excipients.