DUPIXENT

Dupilumab, an interleukin-4 receptor alpha antagonist, is a human monoclonal antibody of the IgG4 subclass that binds to the IL-4Rα subunit and inhibits IL-4 and IL-13 signaling.

Dupilumab has an approximate molecular weight of 147 kDa.

Dupilumab is produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture.

DUPIXENT (dupilumab) Injection is supplied as a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution for subcutaneous injection.

DUPIXENT is provided as either a single-dose pre-filled syringe with needle shield or a single-dose pre-filled pen in a siliconized Type-1 clear glass syringe.

The needle cap is not made with natural rubber latex.

Each 300 mg pre-filled syringe or pre-filled pen delivers 300 mg dupilumab in 2 mL which also contains L-arginine hydrochloride (10.5 mg), L-histidine (6.2 mg), polysorbate 80 (4 mg), sodium acetate (2 mg), sucrose (100 mg), and water for injection, pH 5.9.

Each 200 mg pre-filled syringe or pre-filled pen delivers 200 mg dupilumab in 1.14 mL which also contains L-arginine hydrochloride (12 mg), L-histidine (3.5 mg), polysorbate 80 (2.3 mg), sodium acetate (1.2 mg), sucrose (57 mg), and water for injection, pH 5.9.

Acetary skin infection (eczema).

Carefully used under the supervision of a doctor in the following cases: pregnancy and breastfeeding; congenital or cornea infection; asthma; heart disorders; neuropathy with hyperacid patients.

Mechanism of Action Dupilumab is a human monoclonal IgG4 antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling by specifically binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes.

Dupilumab inhibits

IL-4 signaling via the Type I receptor and both IL-4 and IL-13 signaling through the Type II receptor.

Inflammation driven by

IL-4 and IL-13 is an important component in the pathogenesis of asthma, AD, CRSwNP, EoE, PN, COPD, CSU, BP, and AFRS.

Multiple cell types that express

IL-4Rα (e.g., mast cells, basophils, eosinophils, macrophages, lymphocytes, epithelial cells, goblet cells) and inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines, chemokines) are involved in inflammation.

IL-4Rα with dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE.

The mechanism of dupilumab action has not been definitively established. 12.2 Pharmacodynamics Consistent with inhibition of IL-4 and IL-13 signaling, dupilumab treatment decreased certain biomarkers of inflammation.

In asthma subjects, fractional exhaled nitric oxide (FeNO) and circulating concentrations of eotaxin-3, total IgE, allergen specific IgE, TARC, and periostin were decreased relative to placebo.

Reductions in these biomarkers were comparable for the 300 mg Q2W and 200 mg Q2W regimens.

These markers were near maximal suppression after 2 weeks of treatment, except for IgE which declined more slowly.

These effects were sustained throughout treatment.

The median percent reduction from baseline in total IgE concentrations with dupilumab treatments was 52% at Week 24 (DRI12544) and 70% at Week 52 (QUEST).

FeNO, the mean percent reduction from baseline at Week was 35% and 24% in DRI12544 and QUEST, respectively, and in the overall safety population, the mean FeNO level decreased to 20 ppb.

A continuous decline in total IgE in serum was observed in CSU trials.

In AFRS subjects, total IgE concentrations showed a progressive decline with dupilumab treatment throughout the 52-week treatment period.

Antibody Response to Non-Live Vaccines During DUPIXENT Treatment In a clinical study, adult subjects with AD were treated once weekly for 16 weeks with 300 mg of DUPIXENT (twice the recommended dosing frequency).

After 12 weeks of administration, subjects received a Tdap vaccine and a meningococcal polysaccharide vaccine.

Antibody responses to tetanus toxoid and serogroup C meningococcal polysaccharide were assessed 4 weeks later.

Antibody responses to both tetanus toxoid and serogroup C meningococcal polysaccharide were similar in DUPIXENT-treated and placebo-treated subjects.

Antibody responses to the other active components of both vaccines were not assessed.

Antibody responses to other non-live vaccines were also not assessed. 12.3 Pharmacokinetics The pharmacokinetics of dupilumab is similar in subjects with AD, asthma, CRSwNP, EoE, PN, COPD, CSU, BP, and AFRS.

Following an initial subcutaneous (SC) dose of 600 mg, 400 mg, or 300 mg, dupilumab reached peak mean ± SD concentrations (C max ) of 70.1±24.1 mcg/mL, 41.8±12.4 mcg/mL, or 30.5±9.39 mcg/mL, respectively, by approximately 1 week post dose.

Steady-state concentrations were achieved by

Week 16 following the administration of 600 mg starting dose and 300 mg dose either weekly or Q2W, or 400 mg starting dose and 200 mg dose Q2W, or 300 mg Q2W without a loading dose.

Across clinical trials, the mean ± SD steady-state trough concentrations ranged from 55.3±34.3 mcg/mL to 80.2±35.3 mcg/mL for 300 mg administered Q2W, from 173±75.9 mcg/mL to 195±71.7 mcg/mL for 300 mg administered weekly, and from 29.2±18.7 to 36.5±22.2 mcg/mL for 200 mg administered Q2W.

The bioavailability of dupilumab following a SC dose is similar between AD, asthma, CRSwNP, EoE, PN, COPD, CSU, BP, and AFRS subjects, ranging between 61% and 66%.

The estimated total volume of distribution was approximately 4.8±1.3 L. Elimination The metabolic pathway of dupilumab has not been characterized.

As a human monoclonal

IgG4 antibody, dupilumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

After the last steady-state dose of 300 mg QW, 300 mg Q2W, 200 mg Q2W, 300 mg Q4W, or 200 mg Q4W dupilumab, the median times to non-detectable concentration (<78 ng/mL) ranged from to 13 weeks in adults and pediatric subjects 12 years of age and older.

Population pharmacokinetic analyses indicate the median times to non-detectable concentration are approximately 1.5 times (up to 19 weeks) and 2.5 times (up to 32 weeks) longer in pediatric subjects to 11 years of age and pediatric subjects 6 months to 5 years of age, respectively.

Dupilumab exhibited nonlinear target-mediated pharmacokinetics with exposures increasing in a greater than dose-proportional manner.

The systemic exposure increased by 30-fold when the dose increased 8-fold following a single dose of dupilumab from 75 mg to 600 mg (i.e., 0.25-times to 2-times the recommended dose).

Dupilumab trough concentrations were lower in subjects with higher body weight.

Development of antibodies to dupilumab was associated with lower serum dupilumab concentrations.

A few subjects who had high antibody titers also had no detectable serum dupilumab concentrations.

Based on population pharmacokinetic analysis, age did not affect dupilumab clearance in adults and in pediatric subjects to 17 years of age.

In pediatric subjects 6 months to 5 years of age, clearance increased with age.

No overall differences in the pharmacokinetics of dupilumab were observed between elderly and younger adult subjects.

For pediatric subjects 12 years of age and older with AD receiving every 2 week dosing (Q2W) with either 200 mg (<60 kg) or 300 mg (≥60 kg), the mean ± SD steady-state trough concentration of dupilumab was 54.5±27.0 mcg/mL.

For pediatric subjects to 11 years of age with AD receiving every 2 week dosing (Q2W) with 200 mg (≥30 kg) or every 4 week dosing (Q4W) with 300 mg (<30 kg), mean ± SD steady-state trough concentration was 86.0±34.6 mcg/mL and 98.7±33.2 mcg/mL, respectively.

For pediatric subjects 6 months to 5 years of age with AD receiving every 4 week dosing (Q4W) with 300 mg (≥15 to <30 kg) or 200 mg (≥5 to <15 kg), the mean ± SD steady-state trough concentration was 110±42.8 mcg/mL and 109±50.8 mcg/mL, respectively.

A total of 107 pediatric subjects to 17 years of age with asthma were enrolled in QUEST.

The mean ± SD steady-state trough concentrations of dupilumab were 107±51.6 mcg/mL and 46.7±26.9 mcg/mL, respectively, for 300 mg or 200 mg administered Q2W.

In VOYAGE, dupilumab pharmacokinetics was investigated in 270 subjects with moderate-to-severe asthma following subcutaneous administration of either 100 mg Q2W (for 91 pediatric subjects weighing <30 kg) or 200 mg Q2W (for 179 pediatric subjects weighing ≥30 kg).

The mean ± SD steady-state trough concentration was 58.4±28.0 mcg/mL and 85.1±44.9 mcg/mL, respectively.

Simulation of a 300 mg Q4W subcutaneous dose in pediatric subjects to 11 years of age with body weight of ≥15 to <30 kg resulted in predicted steady-state trough concentrations (98.7±41.0 mcg/mL) and average concentrations higher than the observed trough concentrations and average concentrations of 100 mg Q2W (<30 kg).

Clinical studies have not been conducted in pediatric patients aged 12 years and older with CRSwNP.

Dupilumab exposures are expected to be comparable between adults and pediatric patients aged 12 years and older at the recommended dosage for CRSwNP (300 mg every 2 weeks).

EoE-1, dupilumab pharmacokinetics were investigated in 35 pediatric subjects to 17 years of age, weighing at least 40 kg, with EoE, receiving 300 mg QW.

The mean ± SD steady-state trough concentration of dupilumab was 227±95.3 mcg/mL.

EoE-2 Part A, dupilumab pharmacokinetics were investigated in 20 pediatric subjects to 11 years of age with EoE receiving the following weight-based dosing regimens: ≥15 to <30 kg (200 mg Q2W) and ≥30 to <40 kg (300 mg Q2W).

At Week 16, the mean ± SD steady-state trough concentration of dupilumab was 174±66.2 mcg/mL.

The systemic exposure in pediatric subjects to 11 years of age with a body weight ≥40 kg receiving 300 mg QW is expected to be comparable to adult and pediatric subjects 12 years and older with a body weight ≥40 kg. The systemic exposure in pediatric subjects to 17 years of age with a body weight <40 kg receiving 300 mg Q2W is expected to be comparable to pediatric subjects to 11 years of age.

A total of 12 pediatric subjects to 17 years of age with CSU were enrolled in CUPID (Study A, B, and C), including 6 subjects who received DUPIXENT 200 mg Q2W (≥30 to <60 kg) and 300 mg Q2W (≥60 kg).

At week 24, the mean ± SD observed steady-state trough concentration was 53.6 ± 19.4 mcg/mL, which was within the range of steady-state trough concentrations in adult subjects with CSU who received DUPIXENT 300 mg Q2W.

A total of 20 pediatric subjects to 11 years of age with CSU were enrolled in clinical trials and pharmacokinetic Study PKM16982, including 18 subjects who received DUPIXENT 200 mg Q4W (≥5 to <15 kg), 300 mg Q4W (≥15 to <30 kg), or 200 mg Q2W (≥30 to <60 kg).

At week 24, the mean ± SD steady-state trough concentration was 91.1 ± 39.4 mcg/mL.

A total of 6 pediatric subjects to 17 years of age with AFRS were enrolled in AIMS, including 3 subjects who received DUPIXENT 200 mg Q2W (≥30 to <60 kg) and 300 mg Q2W (≥60 kg).

At week 52, the mean ± SD observed steady-state trough concentration was 72.3 ± 28.8 mcg/mL, which was within the range of steady-state trough concentrations in adult subjects with AFRS who received DUPIXENT 300 mg Q2W.

Drug Interaction Studies An effect of dupilumab on the PK of co-administered medications is not expected.

Based on the population analysis, commonly co-administered medications had no effect on DUPIXENT pharmacokinetics in subjects with moderate-to-severe asthma.

P450 Substrates The effects of dupilumab on the pharmacokinetics of midazolam (metabolized by CYP3A4), warfarin (metabolized by CYP2C9), omeprazole (metabolized by CYP2C19), metoprolol (metabolized by CYP2D6), and caffeine (metabolized by CYP1A2) were evaluated in a study with 12-13 evaluable subjects with AD (a SC loading dose of 600 mg followed by 300 mg SC weekly for six weeks).

No clinically significant changes in

AUC were observed.

The largest effect was observed for metoprolol (CYP2D6) with an increase in AUC of 29%. 12.6 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.

Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the trials described below with the incidence of anti-drug antibodies in other trials, including those of DUPIXENT or of other dupilumab products.

The anti-drug antibody (ADA) and neutralizing antibody (NAb) incidence rates in subjects treated with DUPIXENT are presented in Table 17.

Table 17: Anti-drug Antibody and Neutralizing Antibody Incidence in Subjects Treated with DUPIXENT Indication and Population Dose and Duration of Treatment Anti-drug Antibody (ADA) Neutralizing Antibody NAb Neutralizing potential is assessed only for ADA-positive samples.

The NAb incidence is reported as a percentage of subjects with positive ADA response.

Includes subjects with a treatment-emergent response, defined as a negative or missing result at baseline with at least 1 positive post-baseline re.

Dobelomp is a human

G4-based anti-clothing anti-genulinary subgenic, an injection solution for the treatment of moderate-force A.H., and doctors resort to Dobelomp when regular in situ treatments fail.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Conjunctivitis and Keratitis Psoriasis Arthralgia and Psoriatic Arthritis Parasitic (Helminth).

Infections Most common adverse reactions are: Atopic Dermatitis (incidence ≥1%): injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye, and eosinophilia.

Asthma (incidence ≥1%): injection site reactions, oropharyngeal pain, and eosinophilia.

Polyps (incidence ≥1%): injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.

Esophagitis (incidence ≥2%): injection site reactions, upper respiratory tract infections, arthralgia, and herpes viral infections.

Nodularis (incidence ≥2%): nasopharyngitis, conjunctivitis, herpes infection, dizziness, myalgia, and diarrhea.

Disease (incidence ≥2%): viral infection, headache, nasopharyngitis, back pain, diarrhea, arthralgia, urinary tract infection, local administration reactions, rhinitis, eosinophilia, toothache, and gastritis.

Urticaria (incidence ≥2%): injection site reactions.

Pemphigoid (incidence ≥2%): arthralgia, conjunctivitis, vision blurred, herpes viral infections, keratitis.

Rhinosinusitis: similar to adverse reactions for Chronic Rhinosinusitis with Nasal Polyps.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 practice.

Atopic Dermatitis Adults with Atopic Dermatitis

Three randomized, double-blind, placebo-controlled, multicenter trials (SOLO 1, SOLO 2, and CHRONOS) and one dose-ranging trial (AD-1021) evaluated the safety of DUPIXENT in subjects with moderate-to-severe atopic dermatitis (AD) .

In terms of co-morbid conditions, 48% of the subjects had asthma, 49% had allergic rhinitis, 37% had food allergy, and 27% had allergic conjunctivitis.

In these 4 trials, 1472 subjects were treated with subcutaneous injections of DUPIXENT, with or without concomitant topical corticosteroids (TCS).

A total of 739 subjects were treated with DUPIXENT for at least 1 year in the development program for moderate-to-severe AD.

SOLO 1, SOLO 2, and AD-1021 compared the safety of DUPIXENT monotherapy to placebo through Week 16.

CHRONOS compared the safety of

DUPIXENT + TCS to placebo + TCS through Week 52.

AD-1225 is a multicenter, open-label extension (OLE) trial which assessed the long-term safety of repeat doses of DUPIXENT through 260 weeks of treatment in adults with moderate-to-severe AD who had previously participated in controlled trials of DUPIXENT or had been screened for SOLO 1 or SOLO 2.

The safety data in

AD-1225 reflect exposure to DUPIXENT 200 mg QW, 300 mg QW and 300 mg Q2W in 2677 subjects, including 2254 exposed for at least 52 weeks, 1224 exposed for at least 100 weeks, 561 exposed for at least 148 weeks and 179 exposed for at least 260 weeks.

Weeks to 16 (SOLO 1, SOLO 2, CHRONOS, and AD-1021) In DUPIXENT monotherapy trials (SOLO 1, SOLO 2, and AD-1021) through Week 16, the proportion of subjects who discontinued treatment because of adverse events was 1.9% in both the DUPIXENT 300 mg Q2W and placebo groups.

Table 9 summarizes the adverse reactions that occurred at a rate of at least 1% in the DUPIXENT 300 mg Q2W monotherapy groups, and in the DUPIXENT + TCS group, all at a higher rate than in their respective comparator groups during the first 16 weeks of treatment.

Table 9: Adverse Reactions Occurring in ≥1% of the DUPIXENT Monotherapy Group or the DUPIXENT + TCS Group in the Atopic Dermatitis Trials through Week 16 Adverse Reaction DUPIXENT Monotherapy Pooled analysis of SOLO 1, SOLO 2, and AD-1021.

DUPIXENT + TCS Analysis of CHRONOS where subjects were on background TCS therapy.

DUPIXENT 300 mg Q2W DUPIXENT 600 mg at Week 0, followed by 300 mg every 2 weeks.

DUPIXENT 300 mg Q2W + TCS Placebo + TCS N=529 n (%) N=517 n (%) N=110 n (%) N=315 n (%) Injection site reaction 51 28 11 18 Conjunctivitis Conjunctivitis cluster includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, giant papillary conjunctivitis, eye irritation, and eye inflammation. 51 12 10 15 Blepharitis 2 (<1) 1 (<1) 5 2 Oral herpes 20 8 3 5 Keratitis Keratitis cluster includes keratitis, ulcerative keratitis, allergic keratitis, atopic keratoconjunctivitis, and ophthalmic herpes simplex. 1 (<1) 0 4 0 Eye pruritus 3 1 (<1) 2 2 Other herpes simplex virus infection Other herpes simplex virus infection cluster includes herpes simplex, genital herpes, herpes simplex otitis externa, and herpes virus infection, but excludes eczema herpeticum. 10 6 1 1 (<1) Dry eye 1 (<1) 0 2 1 (<1) Safety through Week 52 (CHRONOS) In the DUPIXENT with concomitant TCS trial (CHRONOS) through Week 52, the proportion of subjects who discontinued treatment because of adverse events was 1.8% in DUPIXENT 300 mg Q2W + TCS group and 7.6% in the placebo + TCS group.

Two subjects discontinued

DUPIXENT because of adverse reactions: atopic dermatitis (1 subject) and exfoliative dermatitis (1 subject).

The safety profile of

DUPIXENT + TCS through Week was generally consistent with the safety profile observed at Week 16.

Safety through 260 Weeks (AD-1225) The long-term safety profile observed in this trial through 260 weeks was generally consistent with the safety profile of DUPIXENT observed in controlled studies.

Subjects 12 Years of Age and Older with Atopic Dermatitis The safety of DUPIXENT was assessed in a trial of 250 pediatric subjects 12 years of age and older with moderate-to-severe AD (AD-1526).

The safety profile of DUPIXENT in these subjects through Week was similar to the safety profile seen in adults with AD.

The long-term safety of

DUPIXENT was assessed in an open-label extension study in pediatric subjects 12 years of age and older with moderate-to-severe AD (AD-1434).

The safety profile of DUPIXENT in subjects followed through Week was similar to the safety profile observed at Week in AD-1526.

The long-term safety profile of

DUPIXENT observed in pediatric subjects 12 years of age and older was consistent with that seen in adults with AD.

Subjects to 11 Years of Age with Atopic Dermatitis The safety of DUPIXENT with concomitant TCS was assessed in a trial of 367 pediatric subjects to 11 years of age with severe AD (AD-1652).

DUPIXENT + TCS in these subjects through Week was similar to the safety profile from trials in adult and pediatric subjects 12 years of age and older with AD.

DUPIXENT ± TCS was assessed in an open-label extension study of 368 pediatric subjects to 11 years of age with AD (AD-1434).

Among subjects who entered this study, 110 (30%) had moderate and 72 (20%) had severe AD at the time of enrollment in AD-1434.

DUPIXENT ± TCS in subjects followed through Week was similar to the safety profile observed through Week in AD-1652.

DUPIXENT ± TCS observed in pediatric subjects to 11 years of age was consistent with that seen in adult and pediatric subjects 12 years of age and older with AD.

Subjects 6 Months to 5 Years of Age with Atopic Dermatitis The safety of DUPIXENT with concomitant TCS was assessed in a trial of 161 pediatric subjects 6 months to 5 years of age with moderate-to-severe AD (AD-1539).

DUPIXENT + TCS in these subjects through Week was similar to the safety profile from trials in adults and pediatric subjects 6 years of age and older with AD.

DUPIXENT ± TCS was assessed in an open-label extension study of 180 pediatric subjects 6 months to 5 years of age with AD (AD-1434).

The majority of subjects were treated with DUPIXENT 300 mg every 4 weeks.

DUPIXENT ± TCS in subjects followed through Week was similar to the safety profile observed through Week in AD-1539.

DUPIXENT ± TCS observed in pediatric subjects 6 months to 5 years of age was consistent with that seen in adults and pediatric subjects 6 years of age and older with AD.

In addition, hand-foot-and-mouth disease was reported in 9 (5%) pediatric subjects and skin papilloma was reported in 4 (2%) pediatric subjects treated with DUPIXENT ± TCS.

These cases did not lead to study drug discontinuation.

Atopic Dermatitis with

Hand and/or Foot Involvement The safety of DUPIXENT was assessed in a 16-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (Liberty-AD-HAFT) in 133 adult and pediatric subjects to 17 years of age with atopic dermatitis with moderate-to-severe hand and/or foot involvement.

In this trial 67 subjects received DUPIXENT, and 66 subjects received placebo.

DUPIXENT-treated subjects received the recommended dosage based on their age and body weight.

The safety profile of DUPIXENT in these subjects through Week was consistent with the safety profile from studies in adult and pediatric subjects 6 months of age and older with moderate-to-severe AD.

Subjects 12 Years of Age and Older with Asthma A total of 2888 adult and pediatric subjects to 17 years of age with moderate-to-severe asthma (AS) were evaluated in 3 randomized, placebo-controlled, multicenter trials of to 52 weeks duration (DRI12544, QUEST, and VENTURE).

Of these, 2678 had a history of 1 or more severe exacerbations in the year prior to enrollment despite regular use of medium to high-dose inhaled corticosteroids plus an additional controller(s) (DRI12544 and QUEST).

A total of 210 subjects with oral corticosteroid-dependent asthma receiving high-dose inhaled corticosteroids plus up to two additional controllers were enrolled (VENTURE).

The safety population (DRI12544 and QUEST) was 12-87 years of age, of which 63% were female, and 82% were White.

DUPIXENT 200 mg or 300 mg was administered subcutaneously Q2W, following an initial dose of 400 mg or 600 mg, respectively.

In DRI12544 and QUEST, the proportion of subjects who discontinued treatment due to adverse events was 4% of the placebo group, 3% of the DUPIXENT 200 mg Q2W group, and 6% of the DUPIXENT 300 mg Q2W group.

Table 10 summarizes the adverse reactions that occurred at a rate of at least 1% in subjects treated with DUPIXENT and at a higher rate than in their respective comparator groups in DRI12544 and QUEST.

Table 10: Adverse Reactions Occurring in ≥1% of Adult and Pediatric Subjects 12 Years of Age and Older with Asthma in the DUPIXENT Groups in DRI12544 and QUEST and Greater than Placebo (6 Month Safety Pool) Adverse Reaction DRI12544 and QUEST DUPIXENT 200 mg Q2W DUPIXENT 300 mg Q2W Placebo N=779 n (%) N=788 n (%) N=792 n (%) Injection site reactions Injection site reactions cluster includes erythema, edema, pruritus, pain, and inflammation. 111 (14%) 144 (18%) 50 (6%) Oropharyngeal pain 13 (2%) 19 (2%) 7 (1%) Eosinophilia Eosinophilia = blood eosinophils ≥3,000 cells/mcL or deemed by the invest.

There is no specific treatment for

DUPIXENT overdose.

In the event of overdosage, contact Poison Control for the latest recommendations and monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.

is contraindicated in patients who have known hypersensitivity to dupilumab or any excipients of DUPIXENT.

Known hypersensitivity to dupilumab or any excipients in DUPIXENT.

is administered by subcutaneous injection.

Recommended dosage is an initial dose of 600 mg (two 300 mg injections), followed by 300 mg given every 2 weeks (Q2W).

Patients 6 Months to 5 Years of Age: Body Weight Recommended Dosage For pediatric patients 6 months to 5 years of age, no initial loading dose is recommended to less than 15 kg 200 mg (one 200 mg injection) every 4 weeks (Q4W) 15 to less than 30 kg 300 mg (one 300 mg injection) every 4 weeks (Q4W) Dosage in Pediatric Patients 6 Years to 17 Years of Age: Body Weight Initial Loading Dose Subsequent Dosage Q2W – every 2 weeks; Q4W – every 4 weeks to less than 30 kg 600 mg (two 300 mg injections) 300 mg Q4W to less than 60 kg 400 mg (two 200 mg injections) 200 mg Q2W 60 kg or more 600 mg (two 300 mg injections) 300 mg Q2W Asthma Dosage in Adult and Pediatric Patients 12 Years and Older: Initial Loading Dose Subsequent Dosage 400 mg (two 200 mg injections) 200 mg every 2 weeks (Q2W) Or 600 mg (two 300 mg injections) 300 mg every 2 weeks (Q2W) Dosage for patients with oral corticosteroid-dependent asthma or with co-morbid moderate-to-severe AD, CRSwNP, or AFRS For pediatric patients 12 years to 17 years of age (≥60 kg) and adults with AFRS 600 mg (two 300 mg injections) 300 mg every 2 weeks (Q2W) Dosage in Pediatric Patients 6 Years to 11 Years of Age: Body Weight Recommended Dosage For pediatric patients 6 years to 11 years of age, no initial loading dose is recommended to less than 30 kg 300 mg every 4 weeks (Q4W) 30 kg or more 200 mg every 2 weeks (Q2W) For pediatric patients 6 years to 11 years old with asthma and co-morbid moderate-to-severe atopic dermatitis, follow the recommended dosage as per Table 2 which includes an initial loading dose.

Recommended dosage for adult and pediatric patients 12 years of age and older is 300 mg given every 2 weeks (Q2W).

Body Weight Recommended Dosage in Adult and Pediatric Patients 1 Year and Older, Weighing At Least 15 kg to less than 30 kg 200 mg every 2 weeks (Q2W) 30 to less than 40 kg 300 mg every 2 weeks (Q2W) 40 kg or more 300 mg every week (QW) Prurigo Nodularis: Recommended dosage for adult patients is an initial dose of 600 mg (two 300 mg injections), followed by 300 mg given every 2 weeks (Q2W).

Recommended dosage for adult patients is 300 mg given every 2 weeks (Q2W).

Patients 2 Years to 5 Years of Age: Body Weight Recommended Dosage For pediatric patients 2 years to 5 years of age with CSU, no initial loading dose is recommended to less than 15 kg 200 mg (one 200 mg injection) every 4 weeks (Q4W) 15 to less than 30 kg 300 mg (one 300 mg injection) every 4 weeks (Q4W) Dosage in Pediatric Patients 6 Years to 17 Years of Age: Body Weight Initial Loading Dose Subsequent Dosage Q2W – every 2 weeks; Q4W – every 4 weeks to less than 30 kg 600 mg (two 300 mg injections) 300 mg Q4W to less than 60 kg 400 mg (two 200 mg injections) 200 mg Q2W 60 kg or more 600 mg (two 300 mg injections) 300 mg Q2W Bullous Pemphigoid: Recommended dosage for adult patients is an initial dose of 600 mg (two 300 mg injections), followed by 300 mg given every other week (Q2W).

DUPIXENT in combination with a tapering course of oral corticosteroids.

Allergic Fungal Rhinosinusitis Dosage in Adults

Recommended dosage is 300 mg given every 2 weeks (Q2W).

Patients 6 Years to 17 Years of Age: Body Weight Recommended Dosage Q2W – every 2 weeks; Q4W – every 4 weeks to less than 30 kg 300 mg Q4W to less than 60 kg 200 mg Q2W 60 kg or more 300 mg Q2W 2.1 Important Administration Instructions DUPIXENT is administered by subcutaneous injection.

DUPIXENT is intended for use under the guidance of a healthcare provider.

Provide proper training to patients and/or caregivers on the preparation and administration of DUPIXENT prior to use according to the "Instructions for Use".

Use of Pre-filled Pen or Pre-filled Syringe The DUPIXENT pre-filled pen is for use in adult and pediatric patients aged 2 years and older.

DUPIXENT pre-filled syringe is for use in adult and pediatric patients aged 6 months and older.

A caregiver or patient 12 years of age and older may inject DUPIXENT using the pre-filled syringe or pre-filled pen.

In pediatric patients 12 years of age and older, administer DUPIXENT under the supervision of an adult.

In pediatric patients 6 months to less than 12 years of age, administer DUPIXENT by a caregiver.

Administration Instructions For patients with

AD, asthma, PN, CSU, and BP taking an initial 600 mg dose, administer each of the two DUPIXENT 300 mg injections at different injection sites.

For patients with

AD, asthma, and CSU taking an initial 400 mg dose, administer each of the two DUPIXENT 200 mg injections at different injection sites.

Administer subcutaneous injection into the thigh or abdomen, except for the 2 inches (5 cm) around the navel.

The upper arm can also be used if a caregiver administers the injection.

Rotate the injection site with each injection.

DO NOT inject

DUPIXENT into skin that is tender, damaged, bruised, or scarred.

DUPIXENT "Instructions for Use" contains more detailed instructions on the preparation and administration of DUPIXENT. 2.2 Vaccination Prior to Treatment Consider completing all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with DUPIXENT. 2.3 Recommended Dosage for Atopic Dermatitis Dosage in Adults The recommended dosage of DUPIXENT for adult patients is an initial dose of 600 mg (two 300 mg injections), followed by 300 mg given every 2 weeks (Q2W).

Patients 6 Months to 5 Years of Age The recommended dosage of DUPIXENT for pediatric patients 6 months to 5 years of age is specified in Table 1.

Table 1: Dosage of DUPIXENT in Pediatric Patients 6 Months to 5 Years of Age with Atopic Dermatitis Body Weight Recommended Dosage For pediatric patients 6 months to 5 years of age with AD, no initial loading dose is recommended. 5 to less than 15 kg 200 mg (one 200 mg injection) every 4 weeks (Q4W) 15 to less than 30 kg 300 mg (one 300 mg injection) every 4 weeks (Q4W) Dosage in Pediatric Patients 6 Years to 17 Years of Age The recommended dosage of DUPIXENT for pediatric patients 6 years to 17 years of age is specified in Table 2.

Table 2: Dosage of DUPIXENT in Pediatric Patients 6 Years to 17 Years of Age with Atopic Dermatitis Body Weight Initial Loading Dose Subsequent Dosage to less than 30 kg 600 mg (two 300 mg injections) 300 mg every 4 weeks (Q4W) 30 to less than 60 kg 400 mg (two 200 mg injections) 200 mg every 2 weeks (Q2W) 60 kg or more 600 mg (two 300 mg injections) 300 mg every 2 weeks (Q2W) Concomitant Topical Therapies DUPIXENT can be used with or without topical corticosteroids.

Topical calcineurin inhibitors may be used, but should be reserved for problem areas only, such as the face, neck, intertriginous and genital areas. 2.4 Recommended Dosage for Asthma Dosage in Adult and Pediatric Patients 12 Years and Older The recommended dosage of DUPIXENT for adult and pediatric patients 12 years of age and older is specified in Table 3.

Table 3: Dosage of DUPIXENT in Adult and Pediatric Patients 12 Years and Older with Asthma Initial Loading Dose Subsequent Dosage 400 mg (two 200 mg injections) 200 mg every 2 weeks (Q2W) Or 600 mg (two 300 mg injections) 300 mg every 2 weeks (Q2W) Dosage for patients with oral corticosteroid-dependent asthma or with co-morbid moderate-to-severe AD, CRSwNP, or AFRS For pediatric patients 12 years to 17 years of age (≥60 kg) and adults with AFRS 600 mg (two 300 mg injections) 300 mg every 2 weeks (Q2W) Dosage in Pediatric Patients 6 Years to 11 Years of Age The recommended dosage of DUPIXENT for pediatric patients 6 years to 11 years of age is specified in Table 4.

Table 4: Dosage of DUPIXENT in Pediatric Patients 6 Years to 11 Years of Age with Asthma Body Weight Recommended Dosage For pediatric patients 6 years to 11 years of age with asthma, no initial loading dose is recommended. 15 to less than 30 kg 300 mg every 4 weeks (Q4W) 30 kg or more 200 mg every 2 weeks (Q2W) For pediatric patients 6 years to 11 years of age with asthma and co-morbid moderate-to-severe AD, follow the recommended dosage as per Table 2 which includes an initial loading dose. 2.5 Recommended Dosage for Chronic Rhinosinusitis with Nasal Polyps The recommended dosage of DUPIXENT for adult and pediatric patients 12 years of age and older is 300 mg given every 2 weeks (Q2W). 2.6 Recommended Dosage for Eosinophilic Esophagitis The recommended dosage of DUPIXENT for adult and pediatric patients 1 year of age and older, weighing at least 15 kg, is specified in Table 5.

Table 5: Dosage of DUPIXENT in Adult and Pediatric Patients 1 Year of Age and Older with Eosinophilic Esophagitis Body Weight Recommended Dosage to less than 30 kg 200 mg every 2 weeks (Q2W) 30 to less than 40 kg 300 mg every 2 weeks (Q2W) 40 kg or more 300 mg every week (QW) 2.7 Recommended Dosage for Prurigo Nodularis The recommended dosage of DUPIXENT for adult patients is an initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every 2 weeks (Q2W). 2.8 Recommended Dosage for Chronic Obstructive Pulmonary Disease The recommended dosage of DUPIXENT for adult patients is 300 mg given every 2 weeks (Q2W). 2.9 Recommended Dosage for Chronic Spontaneous Urticaria Dosage in Adults The recommended dosage of DUPIXENT for adult patients is an initial dose of 600 mg (two 300 mg injections), followed by 300 mg given every 2 weeks (Q2W).

Patients 2 Years to 5 Years of Age The recommended dosage of DUPIXENT for pediatric patients 2 years to 5 years of age is specified in Table 6.

Table 6: Dosage of DUPIXENT in Pediatric Patients 2 Years to 5 Years of Age with Chronic Spontaneous Urticaria Body Weight Recommended Dosage For pediatric patients 2 years to 5 years of age with CSU, no initial loading dose is recommended. 5 to less than 15 kg 200 mg (one 200 mg injection) every 4 weeks (Q4W) 15 to less than 30 kg 300 mg (one 300 mg injection) every 4 weeks (Q4W) Dosage in Pediatric Patients 6 Years to 17 Years of Age The recommended dosage of DUPIXENT for pediatric patients 6 years to 17 years of age is specified in Table 7.

Table 7: Dosage of DUPIXENT in Pediatric Patients 6 Years to 17 Years of Age with Chronic Spontaneous Urticaria Body Weight Initial Loading Dose Subsequent Dosage to less than 30 kg 600 mg (two 300 mg injections) 300 mg every 4 weeks (Q4W) 30 to less than 60 kg 400 mg (two 200 mg injections) 200 mg every 2 weeks (Q2W) 60 kg or more 600 mg (two 300 mg injections) 300 mg every 2 weeks (Q2W) 2.10 Recommended Dosage for Bullous Pemphigoid The recommended dosage of DUPIXENT for adult patients is an initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week (Q2W).

Use DUPIXENT in combination with a tapering course of oral corticosteroids.

Once disease control has occurred, gradually taper corticosteroids after which continue DUPIXENT as monotherapy.

In case of relapse, corticosteroids may be added if medically advisable. 2.11 Recommended Dosage for Allergic Fungal Rhinosinusitis Dosage in Adults The recommended dosage of DUPIXENT for adult patients is 300 mg given every two weeks (Q2W).

Patients 6 Yea.

DUPIXENT (dupilumab) Injection is a clear to slightly opalescent, colorless to pale yellow solution, supplied in single-dose pre-filled syringes with needle shield or pre-filled pens.

The pre-filled syringe with needle shield is designed to deliver: 300 mg of DUPIXENT in 2 mL solution (NDC 0024-5914-00) 200 mg of DUPIXENT in 1.14 mL solution (NDC 0024-5918-00) The pre-filled pen is designed to deliver: 300 mg of DUPIXENT in 2 mL solution (NDC 0024-5915-00) 200 mg of DUPIXENT in 1.14 mL solution (NDC 0024-5919-00) DUPIXENT is available in cartons containing 2 pre-filled syringes with needle shield or 2 pre-filled pens.

Size 300 mg/2 mL (150 mg/mL) Pre-filled Syringe with Needle Shield 200 mg/1.14 mL (175 mg/mL) Pre-filled Syringe with Needle Shield Pack of 2 syringes NDC 0024-5914-01 NDC 0024-5918-01 Pack Size 300 mg/2 mL (150 mg/mL) Pre-filled Pen 200 mg/1.14 mL (175 mg/mL) Pre-filled Pen Pack of 2 pens NDC 0024-5915-02 NDC 0024-5919-02 Storage and Handling DUPIXENT is sterile and preservative-free.

Discard any unused portion.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

If necessary, DUPIXENT may be kept at room temperature up to 25°C (77°F) for a maximum of 14 days.

Do not store above 25°C (77°F).

After removal from the refrigerator, DUPIXENT must be used within 14 days or discarded.

Do not expose

DUPIXENT to heat or direct sunlight.

Do NOT freeze.

Do NOT shake.

DUPIXENT is sterile and preservative-free.

Discard any unused portion.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

If necessary, DUPIXENT may be kept at room temperature up to 25°C (77°F) for a maximum of 14 days.

Do not store above 25°C (77°F).

After removal from the refrigerator, DUPIXENT must be used within 14 days or discarded.

Do not expose

DUPIXENT to heat or direct sunlight.

Do NOT freeze.

Do NOT shake.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to DUPIXENT during pregnancy.

Risk Summary Available data from case reports and case series with DUPIXENT use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

IgG antibodies are known to cross the placental barrier; therefore, DUPIXENT may be transmitted from the mother to the developing fetus.

There are adverse effects on maternal and fetal outcomes associated with asthma in pregnancy.

In an enhanced pre.

• and post-natal developmental study, no adverse developmental effects were observed in offspring born to pregnant monkeys after subcutaneous administration of a homologous antibody against interleukin-4-receptor alpha (IL-4Rα) during organogenesis through parturition at doses up to 10-times the maximum recommended human dose (MRHD) .

The background risk of major birth defects and miscarriage for the indicated populations are unknown.

All pregnancies have a background risk of birth defect, loss or other adverse outcomes.

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.

Maternal and/or Embryo-fetal Risk In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.

The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.

Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester.

Therefore, DUPIXENT may be present in infants exposed in utero.

The potential clinical impact of dupilumab exposure in infants exposed in utero should be considered.

• and post-natal development toxicity study, pregnant cynomolgus monkeys were administered weekly subcutaneous doses of homologous antibody against IL-4Rα up to 10 times the MRHD (on a mg/kg basis of 100 mg/kg/week) from the beginning of organogenesis to parturition.

No treatment-related adverse effects on embryo-fetal toxicity or malformations, or on morphological, functional, or immunological development were observed in the infants from birth through 6 months of age.

Atopic Dermatitis The safety and effectiveness of DUPIXENT have been established in pediatric patients 6 months of age and older with moderate-to-severe AD, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

Use of

DUPIXENT in this is supported by data from the following clinical trials: AD-1526 which included 251 pediatric subjects 12 years of age and older with moderate-to-severe AD.

Of the 251 subjects, 82 were treated with DUPIXENT 200 mg Q2W (<60 kg) or 300 mg Q2W (≥60 kg) and were treated with matching placebo AD-1652 which included 367 pediatric subjects to 11 years of age with severe AD.

Of the 367 subjects, 120 were treated with DUPIXENT 300 mg Q4W + TCS (15 to <30 kg) or 200 mg Q2W + TCS (≥30 kg) and were treated with matching placebo + TCS AD-1539 which included 162 pediatric subjects 6 months to 5 years of age with moderate-to-severe AD.

Of the 162 subjects, 83 were treated with DUPIXENT 200 mg Q4W + TCS (5 to <15 kg) or 300 mg Q4W + TCS (15 to <30 kg) and 79 subjects were assigned to be treated with matching placebo + TCS AD-1434, an open-label extension study that enrolled 275 pediatric subjects 12 years of age and older treated with DUPIXENT ± TCS, 368 pediatric subjects to 11 years of age treated with DUPIXENT ± TCS, and 180 pediatric subjects 6 months to 5 years of age treated with DUPIXENT ± TCS Liberty-AD-HAFT which included 27 pediatric subjects 12 years of age and older with atopic dermatitis with moderate-to-severe hand and/or foot involvement treated with DUPIXENT (N=14) or matching placebo (N=13) The safety and effectiveness were generally consistent between pediatric and adult patients.

In addition, hand-foot-and-mouth disease was reported in 9 (5%) pediatric subjects and skin papilloma was reported in 4 (2%) pediatric subjects 6 months to 5 years of age treated with DUPIXENT ± TCS in AD-1434.

These cases did not lead to study drug discontinuation.

Safety and effectiveness of

DUPIXENT have not been established in pediatric patients younger than 6 months of age with AD.

Asthma The safety and effectiveness of

DUPIXENT for an add-on maintenance treatment in patients with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma have been established in pediatric patients 6 years of age and older.

DUPIXENT for this indication is supported by evidence from adequate and well-controlled studies in adult and pediatric patients 6 years and older.

Subjects to 17 Years of Age: A total of 107 pediatric subjects to 17 years of age with moderate-to-severe asthma were enrolled in QUEST and received either 200 mg (N=21) or 300 mg (N=18) DUPIXENT (or matching placebo either 200 mg [N=34] or 300 mg [N=34]) Q2W.

Asthma exacerbations and lung function were assessed in both pediatric subjects to 17 years of age and adults.

For both the 200 mg and 300 mg Q2W doses, improvements in FEV 1 (LS mean change from baseline at Week 12) were observed (0.36 L and 0.27 L, respectively).

For the 200 mg Q2W dose, subjects had a reduction in the rate of severe exacerbations that was consistent with adults.

Dupilumab exposure was higher in pediatric subjects to 17 years of age than that in adults at the respective dose level which was mainly accounted for by difference in body weight.

The adverse event profile in pediatric subjects to 17 years of age was generally similar to the adults.

Subjects to 11 Years of Age: A total of 408 pediatric subjects to 11 years of age with moderate-to-severe asthma were enrolled in VOYAGE, which evaluated doses of 100 mg Q2W or 200 mg Q2W.

Improvement in asthma exacerbations and lung function were demonstrated.

The effectiveness of

DUPIXENT 300 mg Q4W in subjects to 11 years of age with body weight to <30 kg was extrapolated from efficacy of 100 mg Q2W in VOYAGE with support from population pharmacokinetic analyses showing higher drug exposure levels with 300 mg Q4W.

Subjects who completed the treatment period of the VOYAGE study could participate in the open-label extension study (LTS14424).

Eighteen subjects (≥15 to <30 kg) out of 365 subjects were exposed to 300 mg Q4W in this study, and the safety profile in these eighteen subjects was consistent with that seen in VOYAGE.

Additional safety for

DUPIXENT 300 mg Q4W is based upon available safety information from the pediatric AD indication.

DUPIXENT have not been established in pediatric patients younger than 6 years of age with asthma.

CRSwNP The safety and effectiveness of

DUPIXENT for add-on maintenance treatment in patients with inadequately controlled CRSwNP have been established in pediatric patients aged 12 years and older.

DUPIXENT for this indication is supported by evidence from adequate and well-controlled studies of DUPIXENT as add-on maintenance treatment in adults with inadequately controlled CRSwNP (SINUS-24 and SINUS-52) with the following additional data: Pharmacokinetic (PK) data from adult and pediatric patients aged 12 years and older with moderate-to-severe asthma and adult patients with inadequately controlled CRSwNP Safety data in pediatric patients aged 12 years and older with moderate-to-severe asthma Safety and effectiveness of DUPIXENT have not been established in pediatric patients younger than 12 years of age with CRSwNP.

EoE The safety and effectiveness of DUPIXENT for the treatment of EoE have been established in pediatric subjects 1 year of age and older, weighing at least 15 kg. Use of DUPIXENT in this population is supported by an adequate well-controlled study in adults and 72 pediatric subjects to 17 years of age (Study EoE-1), a clinical study in 61 pediatric subjects to 11 years of age (Study EoE-2), and pharmacokinetic data in adult and pediatric subjects to 17 years of age.

The safety of

DUPIXENT in pediatric subjects to 17 years of age was similar to adults.

DUPIXENT have not been established in pediatric patients younger than 1 year of age, or weighing less than 15 kg, with EoE.

Prurigo Nodularis Safety and effectiveness of

DUPIXENT have not been established in pediatric patients with PN.

Chronic Obstructive Pulmonary Disease The safety and effectiveness of DUPIXENT have not been established in pediatric patients with COPD.

COPD is largely a disease of adult patients.

Chronic Spontaneous Urticaria The safety and effectiveness of DUPIXENT for the treatment of CSU in patients who remain symptomatic despite H1 antihistamine treatment have been established in pediatric patients 2 years of age and older.

DUPIXENT in this indication is supported by evidence from two adequate and well-controlled studies in adults and pediatric patients aged 12 years and older with the following additional data: Pharmacokinetic (PK) data in 6 pediatric patients to 17 years of age, PK data in 18 pediatric patients to 11 years of age, and safety data in pediatric patients in other indications Safety and effectiveness of DUPIXENT have not been established in pediatric patients younger than 2 years of age, and/or weighing less than 5 kg, with CSU.

Bullous Pemphigoid The safety and effectiveness of DUPIXENT have not been established in pediatric patients with BP.

BP is largely a disease of adult patients.

Allergic Fungal Rhinosinusitis The safety and effectiveness of DUPIXENT for the treatment of AFRS in patients who have a history of sino-nasal surgery have been established in pediatric patients 6 years of age and older.

DUPIXENT in this indication is supported by evidence from an adequate and well-controlled study (AIMS) in adults and pediatric patients aged 12 years and older, with the following additional data: Pharmacokinetic (PK) data in 3 pediatric patients 12 years of age and older with AFRS PK and safety data in pediatric patients 6 years to 11 years of age in other indications.

Safety and effectiveness in pediatric patients younger than 6 years of age with AFRS have not been established.

Of the 1539 subjects with AD exposed to DUPIXENT in a dose-ranging study and placebo-controlled trials, 70 subjects were 65 years or older.

Clinical trials of DUPIXENT in

AD did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects.

Of the 1977 subjects with asthma exposed to DUPIXENT, a total of 240 subjects were 65 years or older.

Efficacy and safety in this were similar to the overall study population.

Of the 440 subjects with CRSwNP exposed to DUPIXENT, a total of 79 subjects were 65 years or older.

Clinical studies of DUPIXENT in

EoE did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger adult subjects.

Of the 152 subjects with PN exposed to DUPIXENT, a total of were 65 years or older including 8 subjects 75 years or older.

Clinical trials did not include a sufficient number of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

Of the 1874 subjects with COPD randomized in clinical trials of DUPIXENT, a total of were 65 years or older, while 244 subjects were 75 years or older.

No overall differences in safety or effectiveness of DUPIXENT have been observed between subjects 65 years of age and older and younger adult subjects.

Of the 198 subjects with CSU exposed to DUPIXENT, a total of 30 subjects were 65 years or older, including 7 subjects 75 years or older.

Efficacy and safety in subjects 65 years or older were similar to the overall study population.

Of the 53 subjects with BP exposed to DUPIXENT, a total of were 65 years or older, including 22 subjects 75 years or older.

Ten percent of subjects aged 65 years and older treated with DUPIXENT had an adverse reaction of vision blurred compared to zero in younger adult subjects.

AFRS did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.