Brodalumab

SILIQ ® (brodalumab) is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. SILIQ is a human interleukin-17 receptor A (IL-17RA) antagonist indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. ( 1 )

Administer 210 mg of SILIQ by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. ( 2.2 )

2.1 Tuberculosis Assessment Prior to Initiation of SILIQ Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SILIQ [see Warnings and Precautions ( 5.4 )].

2.2 Dosage The recommended SILIQ dose is 210 mg administered by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. If an adequate response has not been achieved after 12 to 16 weeks of treatment with SILIQ, consider discontinuing therapy. Continued treatment beyond 16 weeks in patients who have not achieved an adequate response is not likely to result in greater success.

2.3 Important Administration Instructions Administer SILIQ subcutaneously. Each prefilled syringe is for single dose only. Instruct patients to review the Medication Guide before use [see Medication Guide] . SILIQ is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject SILIQ when deemed appropriate by a healthcare professional and after proper training in subcutaneous injection technique using the prefilled syringe. Advise patients who are self-administering to inject the full dose and to read the Instructions for Use before administration [see Instructions for Use] . Do not inject SILIQ into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.

2.4 Preparation of SILIQ Prefilled Syringe

• Allow SILIQ prefilled syringe to reach room temperature (approximately 30 minutes) before injecting. Do not warm in any other way. Do not remove the gray needle cap on the prefilled syringe while allowing it to reach room temperature.
• Visually inspect SILIQ for particles and discoloration prior to administration. SILIQ is a clear to slightly opalescent, colorless to slightly yellow solution. Do not use SILIQ if it is cloudy or discolored or if foreign matter is present.
• Instruct patients to use the prefilled syringe and to inject the full amount (1.5 mL), which provides 210 mg of SILIQ, according to the directions provided in the Instructions for Use [see Instructions for Use].

Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. SILIQ is a clear to slightly opalescent, colorless to slightly yellow solution. Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. ( 3 )

SILIQ is contraindicated in patients with:

• Crohn’s disease because SILIQ may cause worsening of disease [see Warnings and Precautions ( 5.7 )] .
• Clinically significant hypersensitivity to brodalumab or to any of the excipients in SILIQ or component of the container. Hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of SILIQ [see Warnings and Precautions ( 5.3 )] .
• Crohn’s disease ( 4 )
• Clinically significant hypersensitivity to brodalumab or to any of the excipients in SILIQ or component of the container ( 4 )

CYP450 Substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Treatment with SILIQ may modulate serum levels of some cytokines. Therefore, upon initiation or discontinuation of SILIQ in patients who are receiving concomitant drugs which are CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) and consider dosage modification of the CYP450 substrate [see Clinical Pharmacology ( 12.3 )].

8.1 Pregnancy Risk Summary There are no human data on SILIQ use in pregnant women to inform a drug-associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, SILIQ may be transmitted from the mother to the developing fetus. In a combined embryofetal development and pre- and postnatal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of brodalumab during organogenesis through parturition at doses up to 26 times the maximum recommended human dose (MRHD) [see Data]. The estimated 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 2 to 4% and 15 to 20%, respectively. Data Animal Data A combined embryofetal development and pre- and postnatal development study was conducted in cynomolgus monkeys administered brodalumab. No brodalumab-related effects on embryofetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from pregnant monkeys administered weekly subcutaneous doses of brodalumab up to 26 times the MRHD from the beginning of organogenesis to parturition (on a mg/kg basis of 90 mg/kg/week).

8.2 Lactation Risk Summary There are no data on the presence of brodalumab in human milk, the effects on the breastfed infant, or the effects on milk production. Brodalumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SILIQ and any potential adverse effects on the breastfed infant from SILIQ or from the underlying maternal condition.

8.4 Pediatric Use The safety and effectiveness of SILIQ have not been evaluated in pediatric patients.

8.5 Geriatric Use Of the 3,066 plaque psoriasis subjects initially randomized to SILIQ in clinical trials, 192 (6%) were ≥ 65 years old and no subjects were ≥ 75 years old. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 years and older was not sufficient to determine whether they responded differently from younger subjects [see Clinical Pharmacology ( 12.3 )].

Risk Summary There are no human data on SILIQ use in pregnant women to inform a drug-associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, SILIQ may be transmitted from the mother to the developing fetus. In a combined embryofetal development and pre- and postnatal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of brodalumab during organogenesis through parturition at doses up to 26 times the maximum recommended human dose (MRHD) [see Data]. The estimated 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 2 to 4% and 15 to 20%, respectively. Data Animal Data A combined embryofetal development and pre- and postnatal development study was conducted in cynomolgus monkeys administered brodalumab. No brodalumab-related effects on embryofetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from pregnant monkeys administered weekly subcutaneous doses of brodalumab up to 26 times the MRHD from the beginning of organogenesis to parturition (on a mg/kg basis of 90 mg/kg/week).

The safety and effectiveness of SILIQ have not been evaluated in pediatric patients.

Of the 3,066 plaque psoriasis subjects initially randomized to SILIQ in clinical trials, 192 (6%) were ≥ 65 years old and no subjects were ≥ 75 years old. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 years and older was not sufficient to determine whether they responded differently from younger subjects [see Clinical Pharmacology ( 12.3 )].

Brodalumab is a human monoclonal IgG2κ antibody directed against human interleukin-17 receptor A (IL-17RA). It is expressed in a Chinese Hamster Ovary (CHO) cell line. Brodalumab is comprised of 1312 amino acids and has an estimated molecular mass of 144,000 Daltons. SILIQ (brodalumab) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution delivered via subcutaneous injection. SILIQ is supplied in a single-dose syringe made from type 1 glass with stainless steel 27G x ½” needle. Each SILIQ single-dose prefilled syringe delivers 1.5 mL of solution containing 210 mg of brodalumab formulated in glutamate (6.5 mg), polysorbate 20 (0.15 mg), proline (36 mg), and Water for Injection, USP at pH 4.8.

12.1 Mechanism of Action Brodalumab is a human monoclonal IgG2 antibody that selectively binds to human IL-17RA and inhibits its interactions with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. IL-17RA is a protein expressed on the cell surface and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. Blocking IL-17RA inhibits IL-17 cytokine-induced responses including the release of pro-inflammatory cytokines and chemokines.

12.2 Pharmacodynamics Elevated levels of IL-17A, IL-17C, and IL-17F are found in psoriatic plaques. Serum IL-17A levels, measured at Weeks 12, 24, and 48 of SILIQ 210 mg every 2 weeks of treatment, were higher than the baseline levels in subjects with moderate to severe plaque psoriasis. The relationship between the pharmacodynamic activity and the mechanism(s) by which brodalumab exerts its clinical effects is unknown.

12.3 Pharmacokinetics Absorption Following a single subcutaneous dose of 210 mg in subjects with plaque psoriasis, brodalumab reached peak mean (±SD) serum concentration (C max ) of 13.4±7.3 mcg/mL by approximately 3 days post-dose. The mean (±SD) area-under-the-concentration-time curve (AUC) of brodalumab was 111±64 mcg

• day/mL. Following multiple subcutaneous doses of 210 mg every 2 weeks, steady-state was achieved by Week 4. The mean (±SD) C max was 20.6±14.6 mcg/mL and the mean (±SD) AUC over the 2-week dosing interval was 227±167 mcg
• day/mL. Following subcutaneous administration, brodalumab bioavailability was approximately 55%. Distribution Following a single subcutaneous administration of brodalumab 210 mg in subjects with plaque psoriasis, the mean (±SD) apparent volume of distribution (Vz/F) of brodalumab was 8.9±9.4 L. Elimination The metabolic pathway of brodalumab has not been characterized. As a human monoclonal IgG2 antibody, brodalumab is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG. Following a single subcutaneous administration of brodalumab 210 mg in subjects with plaque psoriasis, the mean (±SD) apparent total clearance (CL/F) was 3.0±3.5 L/day. The clearance of brodalumab increased with decreasing doses due to nonlinear elimination. Dose Linearity Brodalumab exhibited nonlinear pharmacokinetics with exposures that increased greater than dose-proportionally over a dose range from 140 mg (approximately 0.67 times the recommended dose) to 350 mg (approximately 1.67 times the recommended dose) following subcutaneous administrations in subjects with plaque psoriasis. Weight Brodalumab trough concentrations were lower in subjects with higher body weight. Specific Populations Hepatic or Renal Impairment No trials were conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of brodalumab. Age: Geriatric Population Population pharmacokinetic analysis indicated that age did not significantly influence the clearance of brodalumab in subjects with plaque psoriasis. Subjects who were 65 years or older had a similar brodalumab clearance as compared to subjects less than 65 years old. Drug Interaction Studies In subjects with plaque psoriasis, one week following a single subcutaneous administration of 210 mg brodalumab, the exposure of midazolam (CYP3A4 substrate) was increased by 24% [see Drug Interactions ( 7 )].

Brodalumab is a human monoclonal IgG2 antibody that selectively binds to human IL-17RA and inhibits its interactions with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. IL-17RA is a protein expressed on the cell surface and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. Blocking IL-17RA inhibits IL-17 cytokine-induced responses including the release of pro-inflammatory cytokines and chemokines.

Elevated levels of IL-17A, IL-17C, and IL-17F are found in psoriatic plaques. Serum IL-17A levels, measured at Weeks 12, 24, and 48 of SILIQ 210 mg every 2 weeks of treatment, were higher than the baseline levels in subjects with moderate to severe plaque psoriasis. The relationship between the pharmacodynamic activity and the mechanism(s) by which brodalumab exerts its clinical effects is unknown.

Absorption Following a single subcutaneous dose of 210 mg in subjects with plaque psoriasis, brodalumab reached peak mean (±SD) serum concentration (C max ) of 13.4±7.3 mcg/mL by approximately 3 days post-dose. The mean (±SD) area-under-the-concentration-time curve (AUC) of brodalumab was 111±64 mcg

• day/mL. Following multiple subcutaneous doses of 210 mg every 2 weeks, steady-state was achieved by Week 4. The mean (±SD) C max was 20.6±14.6 mcg/mL and the mean (±SD) AUC over the 2-week dosing interval was 227±167 mcg
• day/mL. Following subcutaneous administration, brodalumab bioavailability was approximately 55%. Distribution Following a single subcutaneous administration of brodalumab 210 mg in subjects with plaque psoriasis, the mean (±SD) apparent volume of distribution (Vz/F) of brodalumab was 8.9±9.4 L. Elimination The metabolic pathway of brodalumab has not been characterized. As a human monoclonal IgG2 antibody, brodalumab is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG. Following a single subcutaneous administration of brodalumab 210 mg in subjects with plaque psoriasis, the mean (±SD) apparent total clearance (CL/F) was 3.0±3.5 L/day. The clearance of brodalumab increased with decreasing doses due to nonlinear elimination. Dose Linearity Brodalumab exhibited nonlinear pharmacokinetics with exposures that increased greater than dose-proportionally over a dose range from 140 mg (approximately 0.67 times the recommended dose) to 350 mg (approximately 1.67 times the recommended dose) following subcutaneous administrations in subjects with plaque psoriasis. Weight Brodalumab trough concentrations were lower in subjects with higher body weight. Specific Populations Hepatic or Renal Impairment No trials were conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of brodalumab. Age: Geriatric Population Population pharmacokinetic analysis indicated that age did not significantly influence the clearance of brodalumab in subjects with plaque psoriasis. Subjects who were 65 years or older had a similar brodalumab clearance as compared to subjects less than 65 years old. Drug Interaction Studies In subjects with plaque psoriasis, one week following a single subcutaneous administration of 210 mg brodalumab, the exposure of midazolam (CYP3A4 substrate) was increased by 24% [see Drug Interactions ( 7 )].

, Mutagenesis, Impairment of Fertility Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of SILIQ. The published literature is mixed on the potential effects on malignancy risk due to the inhibition of the IL-17RA, the pharmacological action of SILIQ. Some published literature suggests that IL-17A directly promotes cancer cell invasion, which suggests a potential beneficial effect of SILIQ. However, other reports indicate IL-17A promotes T-cell mediated tumor rejection, which suggests a potential adverse effect by SILIQ. However, inhibition of the IL-17RA with SILIQ has not been studied in these models. Therefore, the relevance of experimental findings in these models for malignancy risk in humans is unknown. In cynomolgus monkeys, there were no effects on fertility parameters such as changes in reproductive organs or sperm analysis following subcutaneous administration of brodalumab at dose levels up to 90 mg/kg/week for 6 months (26 times the MRHD on a mg/kg basis). The monkeys were not mated in this study to evaluate effects on fertility.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use ) before the patient starts using SILIQ, and each time the prescription is renewed, as there may be new information they need to know. Suicidal Thoughts and Behavior Instruct patients and their caregivers to monitor for the emergence of suicidal thoughts and behavior and promptly seek medical attention if the patient experiences suicidal thoughts, new or worsening depression, anxiety, or other mood changes [see Warnings and Precautions ( 5.1 )]. Instruct patients to carry the wallet card provided and to call the National Suicide Prevention Lifeline at 1-800-273-8255 if they experience suicidal thoughts. SILIQ REMS Program Because of the observed suicidal thoughts and behavior in subjects treated with SILIQ, SILIQ is available only through a restricted program called the SILIQ REMS Program [see Warnings and Precautions ( 5.2 )]. Inform the patient of the following:

• Patients must enroll in the program [see Warnings and Precautions ( 5.1 , 5.2 )].
• Patients will be given a SILIQ Patient Wallet Card that they should carry with them at all times. This card describes symptoms which, if experienced, should prompt the patient to immediately seek medical evaluation. Advise the patient to show the SILIQ Patient Wallet Card to other treating healthcare providers. SILIQ is available only from certified pharmacies participating in the program. Therefore, provide patients with the telephone number and website for information on how to obtain the product. Hypersensitivity Reactions Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions ( 5.3 )] . Infections Inform patients that SILIQ may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to their healthcare providers and to contact their healthcare providers if they develop any signs or symptoms of infection [see Warnings and Precautions ( 5.4 )]. Eczematous Eruptions Inform patients that skin reactions resembling eczema may occur with the use of SILIQ. Instruct patients to seek medical advice if they develop signs or symptoms of eczema [see Warnings and Precautions ( 5.6 )] . Crohn’s Disease Instruct patients to seek medical advice if they develop signs and symptoms of Crohn’s disease [see Warnings and Precautions ( 5.7 )]. Immunization Instruct patients to inform their healthcare provider that they are taking SILIQ prior to a potential vaccination [see Warnings and Precautions ( 5.8 )] . Instructions for Injection Instruct the patient to perform the first self-injection under the guidance and supervision of a qualified healthcare professional for proper training in subcutaneous injection technique. Instruct patients who are self-administering to inject the full dose of SILIQ [see Dosage and Administration ( 2.2 ) and Instructions for Use]. Instruct patients or caregivers in the technique of proper syringe and needle disposal [see Instructions for Use]. Distributed by: Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Bausch Health Ireland, Limited Dublin, Leinster, Ireland 24 U.S. License Number: 2365 Patented. See https://patents.ortho-dermatologics.com for US patent information. SILIQ is a registered trademark of Bausch Health Companies Inc. or its affiliates. © 2026 Bausch Health Companies Inc. or its affiliates 9643803