ADULT SAFETY PROFILE

For the treatment of adults with uncontrolled moderate-to-severe atopic dermatitis,

Demonstrated long-term safety profile

The 52-week safety profile of DUPIXENT + TCS in adults was generally
consistent with the Week 16 adult safety profile1

Adverse reactions occurring in ≥1% of adult patients through Week 161
Injection site reaction
DUPIXENTc
(n=529) (%)
10%
PLACEBO
(n=517) (%)
5%
Conjunctivitisd
DUPIXENTc
(n=529) (%)
10%
PLACEBO
(n=517) (%)
2%
Blepharitis
DUPIXENTc
(n=529) (%)
<1%
PLACEBO
(n=517) (%)
<1%
Oral herpes
DUPIXENTc
(n=529) (%)
4%
PLACEBO
(n=517) (%)
2%
Keratitise
DUPIXENTc
(n=529) (%)
<1%
PLACEBO
(n=517) (%)
0%
Eye pruritus
DUPIXENTc
(n=529) (%)
1%
PLACEBO
(n=517) (%)
<1%
Oral herpes simplex virus infectionf
DUPIXENTc
(n=529) (%)
2%
PLACEBO
(n=517) (%)
1%
Dry eye
DUPIXENTc
(n=529) (%)
<1%
PLACEBO
(n=517) (%)
0%
Injection site reaction
DUPIXENT + TCSc
(n=110) (%)
10%
PLACEBO + TCS
(n=315) (%)
6%
Conjunctivitisd
DUPIXENT + TCSc
(n=110) (%)
9%
PLACEBO + TCS
(n=315) (%)
5%
Blepharitis
DUPIXENT + TCSc
(n=110) (%)
5%
PLACEBO + TCS
(n=315) (%)
1%
Oral herpes
DUPIXENT + TCSc
(n=110) (%)
3%
PLACEBO + TCS
(n=315) (%)
2%
Keratitise
DUPIXENT + TCSc
(n=110) (%)
4%
PLACEBO + TCS
(n=315) (%)
0%
Eye pruritus
DUPIXENT + TCSc
(n=110) (%)
2%
PLACEBO + TCS
(n=315) (%)
1%
Oral herpes simplex virus infectionf
DUPIXENT + TCSc
(n=110) (%)
1%
PLACEBO + TCS
(n=315) (%)
<1%
Dry eye
DUPIXENT + TCSc
(n=110) (%)
2%
PLACEBO + TCS
(n=315) (%)
<1%

aPooled analysis of SOLO 1, SOLO 2, and AD-1021 (phase 2 dose-ranging study).

bAnalysis of CHRONOS in which subjects were on background TCS therapy.

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

dConjunctivitis cluster includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, giant papillary conjunctivitis, eye irritation, and eye inflammation.

eKeratitis cluster includes keratitis, ulcerative keratitis, allergic keratitis, atopic keratoconjunctivitis, and ophthalmic herpes simplex.

fOther herpes simplex virus infection cluster includes herpes simplex, genital herpes, herpes simplex otitis externa, and herpes virus infection, but excludes eczema herpeticum.

  • Most patients experiencing conjunctivitis recovered or were recovering during the treatment period1

Select adverse events in the 52-week trial in adults

  • The rate of serious adverse events with DUPIXENT + TCS was comparable to placebo + TCS (4% vs 5%, respectively)2
  • Keratitis was reported in 4% of the DUPIXENT + TCS group and in 0% of the placebo + TCS group1
  • Conjunctivitis was reported in 16% of the DUPIXENT + TCS group and in 9% of the placebo group + TCS group1
Numerically fewer patients treated with DUPIXENT developed skin infections compared with placebo2
  • 11% vs 18% of adults in CHRONOS, respectively

Discontinuation rates in adults due to adverse events with DUPIXENT with or without TCS were comparable to those with placebo1
  • 1.9% of patients treated with DUPIXENT discontinued treatment through Week 16 vs 1.9% of patients treated with placebo through Week 16 (SOLO 1, SOLO 2, and AD-1021)
  • Similar discontinuation rates occurred at Week 52 in CHRONOS (1.8% with DUPIXENT + TCS vs 7.6% with placebo + TCS)

Patients should discontinue DUPIXENT if a clinically significant hypersensitivity reaction occurs or until a parasitic (helminth) infection resolves in a patient who does not respond to anti-helminth treatment.1

Avoid use of live vaccines in patients treated with DUPIXENT1


Safety data collected from three phase 3 trials and one dose-ranging trial (AD-1021) (N=2304)1,2

  • 49% had allergic rhinitis
  • 37% had food allergy
  • 27% had allergic conjunctivitis

Safety and efficacy of DUPIXENT have not been established in the treatment of these conditions.1

Important considerations

SAFETY FINDINGS OF DUPIXENT OPEN-LABEL EXTENSION STUDY IN ADULTS FOR UP TO ≈3 YEARS
(AD-1225)3

  • The long-term safety profile observed in this trial through 148 weeks (≈3 years) was generally consistent with the safety profile of DUPIXENT observed in controlled studies
  • 3.5% of patients discontinued due to treatment-emergent AEs in the OLE study
    • Study description: The safety data in this open-label extension study reflects exposure to DUPIXENT in 2677 subjects, including 2254 exposed for at least 52 weeks, 1192 exposed for at least 100 weeks, and 357 exposed for at least 148 weeks. In AD-1225, 99.7% of subjects were exposed to DUPIXENT 300 mg weekly dosing (QW)

    • In DUPIXENT clinical trials, DUPIXENT 300 mg QW did not demonstrate additional treatment benefit over DUPIXENT 300 mg Q2W

    • Limitations of this OLE study included, but were not limited to: no control arm, DUPIXENT-treated patients with serious adverse events or adverse events that led to study drug discontinuation in the parent study were excluded, and just over half of the patients used concomitant TCS/TCI
TCI, topical calcineurin inhibitors; TCS, topical corticosteroids.

NO BOXED WARNING1
SELECT IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

  • Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, serum sickness or serum sickness-like reactions, angioedema, generalized urticaria, rash, erythema nodosum, and erythema multiforme have been reported. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT

NOT METABOLIZED THROUGH THE LIVER OR EXCRETED THROUGH THE KIDNEYS1

  • No known drug-to-drug interactions

Please see additional Warnings and Precautions in the Prescribing Information and Important Safety Information below.

Other attributes1

DUPIXENT IS NOT AN IMMUNOSUPPRESSANT AND AVOIDS BROAD IMMUNOSUPPRESSION

  • It is unknown if DUPIXENT will influence the immune response against helminth infections

NO REQUIREMENT FOR INITIAL LAB TESTING OR ONGOING LAB MONITORING,
according to the Prescribing Information

References:

  1. DUPIXENT Prescribing Information.
  2. Data on file, Regeneron Pharmaceuticals, Inc.
  3. Beck LA, Thaçi D, Deleuran M, et al. Dupilumab provides favorable safety and sustained efficacy for up to 3 years in an open-label study of adults with moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2020;21(4):567-577.
Important Safety
Information and Indications

CONTRAINDICATION: DUPIXENT is contraindicated in patients with known hypersensitivity to dupilumab or any of its excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, serum sickness or serum sickness-like reactions, angioedema, generalized urticaria, rash, erythema nodosum, and erythema multiforme have been reported. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT.

Conjunctivitis and Keratitis: Conjunctivitis and keratitis occurred more frequently in atopic dermatitis subjects who received DUPIXENT compared to those who received placebo, with conjunctivitis being the most frequently reported eye disorder. Conjunctivitis also occurred more frequently in chronic rhinosinusitis with nasal polyposis subjects who received DUPIXENT compared to those who received placebo. Conjunctivitis and keratitis have been reported with DUPIXENT in postmarketing settings, predominantly in atopic dermatitis patients. Some patients reported visual disturbances (e.g. blurred vision) associated with conjunctivitis or keratitis. Advise patients to report new onset or worsening eye symptoms to their healthcare provider. Consider ophthalmological examination for patients who develop conjunctivitis that does not resolve following standard treatment or signs and symptoms suggestive of keratitis, as appropriate.

Eosinophilic Conditions: Patients being treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis (EGPA), conditions which are often treated with systemic corticosteroid therapy. These events may be associated with the reduction of oral corticosteroid therapy. Healthcare providers should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Cases of eosinophilic pneumonia were reported in adult subjects who participated in the asthma development program and cases of vasculitis consistent with EGPA have been reported with DUPIXENT in adult subjects who participated in the asthma development program as well as in adult subjects with co-morbid asthma in the CRSwNP development program. A causal association between DUPIXENT and these conditions has not been established.

Acute Asthma Symptoms or Deteriorating Disease: Do not use DUPIXENT to treat acute asthma symptoms, acute exacerbations, acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of DUPIXENT.

Risk Associated with Abrupt Reduction of Corticosteroid Dosage: Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon initiation of DUPIXENT. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a healthcare provider. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Patients with Co-morbid Asthma: Advise patients with atopic dermatitis or CRSwNP who have co-morbid asthma not to adjust or stop their asthma treatments without consultation with their physicians.

Arthralgia: Arthralgia has been reported with the use of DUPIXENT with some patients reporting gait disturbances or decreased mobility associated with joint symptoms; some cases resulted in hospitalization. Advise patients to report new onset or worsening joint symptoms. If symptoms persist or worsen, consider rheumatological evaluation and/or discontinuation of DUPIXENT.

Parasitic (Helminth) Infections: It is unknown if DUPIXENT will influence the immune response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with DUPIXENT. If patients become infected while receiving treatment with DUPIXENT and do not respond to anti-helminth treatment, discontinue treatment with DUPIXENT until the infection resolves. Helminth infections (5 cases of enterobiasis and 1 case of ascariasis) were reported in pediatric patients 6 to 11 years old in the pediatric asthma development program.

Vaccinations: Consider completing all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating DUPIXENT. Avoid use of live vaccines in patients treated with DUPIXENT.

ADVERSE REACTIONS:
  • Atopic dermatitis: The most common adverse reactions (incidence ≥1% at Week 16) in adult patients are injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, and dry eye. The safety profile in children and adolescents through Week 16 was similar to that of adults with atopic dermatitis. In an open-label extension study, the long-term safety profile of DUPIXENT in adolescents and children observed through Week 52 was consistent with that seen in adults with atopic dermatitis.
  • Asthma: The most common adverse reactions (incidence ≥1%) are injection site reactions, oropharyngeal pain, and eosinophilia.
  • Chronic rhinosinusitis with nasal polyposis: The most common adverse reactions (incidence ≥1%) are injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.
USE IN SPECIFIC POPULATIONS
  • Pregnancy: A pregnancy exposure registry monitors pregnancy outcomes in women exposed to DUPIXENT during pregnancy. To enroll or obtain information call 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/dupixent/. 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. Human IgG antibodies are known to cross the placental barrier; therefore, DUPIXENT may be transmitted from the mother to the developing fetus.
  • Lactation: There are no data on the presence of DUPIXENT in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DUPIXENT and any potential adverse effects on the breastfed child from DUPIXENT or from the underlying maternal condition.

Please see accompanying full Prescribing Information.


Indications

Atopic Dermatitis: DUPIXENT is indicated for the treatment of adult and pediatric patients aged 6 years and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids.

Asthma: DUPIXENT is indicated as an add-on maintenance treatment of adult and pediatric patients aged 6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma. Limitation of Use: DUPIXENT is not indicated for the relief of acute bronchospasm or status asthmaticus.

Chronic rhinosinusitis with nasal polyposis (CRSwNP): DUPIXENT is indicated as an add-on maintenance treatment in adult patients with inadequately controlled CRSwNP.