MOA: Mechanism of action

DUPIXENT is the only dual inhibitor of IL-4 and IL-13 signaling, inhibiting two key sources of local and systemic Type 2 inflammation in asthma1-3,a

a The mechanism of dupilumab action in asthma has not been definitively established.1

Make DUPIXENT your first-choice biologic for appropriate asthma patients with Type 2 inflammation

How DUPIXENT Works

DUPIXENT blocks the IL-4 and IL-13 signaling pathways, two key sources of Type 2 inflammation in asthma.1,2,4,5

Type 2 inflammation occurs in up to 50% to 84% of adult patients with asthma and plays an important role in the pathogenesis of asthma.

The Type 2 inflammatory pathway encompasses both allergic and eosinophilic inflammation.

Disruption of airway epithelium barrier functions along with allergen uptake by dendritic cells and activation of T cells help drive Type 2 inflammation in asthma. There are multiple cell types and mediators involved in Type 2 inflammation—including IL-4 and IL-13. IL-4 drives Th2 cell differentiation and mediates the production of Type 2 cytokines.

IL-4 and IL-13 play an important role in class switching of B cells to produce IgE, a key component of allergic inflammation.

IL-13 mediates goblet cell hyperplasia and increased mucus secretion and promotes airway obstruction, bronchial hyperreactivity, smooth muscle hypertrophy, airway remodeling, and stimulation of nitric oxide synthase to produce nitric oxide.

IL-4 and IL-13 drive the trafficking of eosinophils to sites of inflammation and IL-5 mediates the differentiation of eosinophils in bone marrow, which contributes to eosinophilic inflammation.

IL-4 and IL-13 are two key cytokines that contribute to allergic and eosinophilic inflammation.

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.

DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling, impacting two of the sources that mediate allergic and eosinophilic inflammation.

[The mechanism of DUPIXENT action in asthma has not been definitively established.]

In the inflammatory process, IL-4 binds the IL-4Rα subunit, and IL-13 binds the IL-13Rα1 subunit.

DUPIXENT binds to IL-4Rα, blocking IL-4 and IL-13 intracellular signaling; this results in reduced expression of proinflammatory cytokines, ultimately leading to decreased total and specific IgE, decreased FeNO, and a transient increase in blood eosinophils.

DUPIXENT blocks the IL-4/IL-13 pathway and decreases markers of Type 2 inflammation, including IgE, in which there was up to 70% reduction in total IgE from baseline and a reduction in eosinophilic lung inflammation, despite the presence of normal or increased blood eosinophil levels.

DUPIXENT also reduced levels of FeNO by blocking IL-13, which is responsible for stimulating nitric oxide synthase to produce nitric oxide.

Based on a study of the general asthma population approximately 7 out of 10 asthma patients had an eosinophilic phenotype or an overlap of eosinophilic and allergic phenotypes.

DUPIXENT is indicated for adult and pediatric patients aged 6 years and older with moderate-to-severe asthma with an eosinophilic phenotype and is the only biologic indicated for an OCS-dependent asthma population.

DUPIXENT is a novel biologic that inhibits IL-4 and IL-13 signaling, two of the sources of inflammation in asthma.

Important Safety
Information and Indication

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.

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 chronic rhinosinusitis with nasal polyposis 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.

Arthralgia: Arthralgia has been reported with 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 the 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: The most common adverse reactions (incidence ≥1%) in patients with asthma are injection site reactions, oropharyngeal pain, and eosinophilia.

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.

Indication

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.

DUPIXENT IS NOT AN IMMUNOSUPPRESSANT1

DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling1,a

IL-4 and IL-13 are key drivers of local and systemic Type 2 inflammation, which can lead to poor asthma control1-5

Only DUPIXENT targets both IL-4 and IL-13 signaling, two key sources of local and systemic Type 2 inflammation1-3,a

a The mechanism of dupilumab action in asthma has not been definitively established.1

DUPIXENT decreased systemic and local Type 2 inflammatory biomarkers1,3,4,6-8

Markers of

Systemic Inflammation

BLOOD EOSINOPHILS

Up to 35% median percent reduction in blood eosinophil levels from baseline at Week 96.b DUPIXENT trials enrolled patients with eosinophil levels up to 1500 cells/μL

TOTAL IgE

Up to 83% reduction from baseline at Week 96b

Marker of

Local Inflammation

FeNO

(a marker of lung inflammation)

Up to 35% reduction from baseline by Week 2c

Elevations in eosinophil count observed in a subset of patients were generally transient in nature. Correlations between DUPIXENT pharmacodynamic data and efficacy endpoints have not been established.
This is not a complete list of biomarkers that may be impacted by DUPIXENT.

b TRAVERSE OLE.

c DRI12544.

The GINA guidelines identify FeNO ≥20 ppb and/or EOS ≥150 cells/µL as markers of Type 2 inflammation9

FeNO, fractional exhaled nitric oxide; GINA, Global Initiative for Asthma; NO, nitric oxide; OLE, open-label extension.

References:

  1. DUPIXENT Prescribing Information.
  2. Corren J. Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 2013;13(5):415-420.
  3. Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.
  4. Robinson D, Humbert M, Buhl R, et al. Revisiting type 2-high and type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-175.
  5. Hammad H, Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol. 2008;8(3):193-204.
  6. Data on file, Sanofi US. QUEST CSR, 2017.
  7. Data on file, Sanofi US. LIBERTY ASTHMA TRAVERSE CSR, 2020.
  8. Wechsler ME, Ford LB, Maspero JF, et al. Dupilumab long-term safety and efficacy in patients with asthma: LIBERTY ASTHMA TRAVERSE. Poster presented at: 30th International Congress of the European Respiratory Society; September 7-9, 2020.
  9. Global Initiative for Asthma. Treating asthma to control symptoms and minimize risk. In: Global Strategy for Asthma Management and Prevention. Updated 2021. Accessed January 13, 2022. https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf

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

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.

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.