Study Designs

DUPIXENT clinical trials enrolled patients
with and without prior
sino-nasal surgery
or SCS use

The Largest Clinical Trial Program Conducted for Chronic Rhinosinusitis with Nasal Polyps

All primary and key secondary endpoints were met with statistical significance1-3

Patients enrolled were continued on background INCS throughout the duration of both trials
SINUS-24(N=276) 24 WEEKS
Randomized

DUPIXENT + INCS
300 mg Q2W for 24 weeks (n=143)
Placebo + INCS for 24 weeks (n=133)

Study population

Adults (≥18 years) on background INCSc with CRSwNP despite prior sino-nasal surgery or prior treatment with, or who were ineligible to receive or were intolerant to, systemic corticosteroids in the past 2 years


Patients with chronic rhinosinusitis without nasal polyposis were not included in these trials


Rescue with systemic corticosteroids or surgery was allowed at investigators’ discretion


The total population of patients in SINUS-24 and SINUS-52 was unrestricted by minimum baseline blood eosinophil count

Coprimary endpoints
Change from baseline at Week 24 in:
  • Nasal congestion/obstruction (NC) score averaged over 28 days
  • Bilateral endoscopic nasal polyp score (NPS)
Key secondary endpoints
Change from baseline at Week 24 in:
  • Daily loss of smell score
  • LMK-CT score
  • SNOT-22 score
  • UPSIT score
Additional endpoints
Change from baseline at Week 24 in FEV1 and ACQ-6 scores in patients with co-existing asthma
Prespecified pooled analysis
Change from baseline at Week 52 in proportion of patients requiring systemic corticosteroids or sino-nasal surgery
SINUS-52(N=448) 52 WEEKS
Randomized

DUPIXENT + INCS
300 mg Q2W for 52 weeks (n=150)a

DUPIXENT + INCS
300 mg Q2W for 24 weeks, followed by Q4Wb through Week 52 (n=145)a
Placebo + INCS for 52 weeks (n=153)

Study population

Adults (≥18 years) on background INCSc with CRSwNP despite prior sino-nasal surgery or prior treatment with, or who were ineligible to receive or were intolerant to, systemic corticosteroids in the past 2 years

Patients with chronic rhinosinusitis without nasal polyposis were not included in these trials

Rescue with systemic corticosteroids or surgery was allowed at investigators’ discretion

The total population of patients in SINUS-24 and SINUS-52 was unrestricted by minimum baseline blood eosinophil count

Coprimary endpoints
Change from baseline at Week 24 in:
  • Nasal congestion/obstruction (NC) score averaged over 28 days
  • Bilateral endoscopic nasal polyps score (NPS)
Key secondary endpoints
Other secondary endpoints
Change from baseline at Week 52 in:
  • Daily loss of smell score
  • LMK-CT score
  • UPSIT score
Additional endpoints
Change from baseline at Week 24 in FEV1 and ACQ-6 scores in patients with co-existing asthma
Prespecified pooled analysis
Change from baseline at Week 52 in proportion of patients requiring systemic corticosteroids or sino-nasal surgery

aIn SINUS-52, data from baseline to Week 24 are pooled from DUPIXENT Q2W treatment arms (n=295).

bThe recommended dose of DUPIXENT for adult patients with CRSwNP is 300 mg given subcutaneously every other week.

cAll patients in the placebo and DUPIXENT arms were on a background therapy of INCS, mometasone furoate nasal spray.

All primary and key secondary endpoints were met with statistical significance1-3

Patient demographics1

SINUS-24: 24 WEEKS (N=276)–Mean age: 50 years; male: 57%; mean CRSwNP duration: 11 years; patients with ≥1 prior surgery: 72%; patients with SCS use in previous 2 years: 65%; mean bilateral endoscopic NPS,d range 0-8: 5.8; mean NC score,d range 0-3: 2.4; mean LMK sinus CT total score,d range 0-24: 19; mean loss of smell scored (AM), range 0-3: 2.7; mean SNOT-22 total score,d range 0-110: 49.4; mean blood eosinophil count: 440 cells/μL; mean total IgE: 212 IU/mL; atopic medical history, overall: 75%; asthma: 58%; NSAID-ERD: 30%.

SINUS-52: 52 WEEKS (N=448)–Mean age: 52 years; male: 62%; mean CRSwNP duration: 11 years; patients with ≥1 prior surgery: 58%; patients with SCS use in previous 2 years: 80%; mean bilateral endoscopic NPS,d range 0-8: 6.1; mean NC score,d range 0-3: 2.4; mean LMK sinus CT total score,d range 0-24: 18; mean loss of smell scored (AM), range 0-3: 2.8; mean SNOT-22 total score,d range 0-110: 51.9; mean blood eosinophil count: 430 cells/μL; mean total IgE: 240 IU/mL; atopic medical history, overall: 82%; asthma: 60%; NSAID-ERD: 27%.

~79% of patients enrolled in both trials had atopic diseases.

In SINUS-24 and SINUS-52, all subjects had evidence of sinus opacification on the LMK sinus CT scan, and 73% to 90% of subjects had opacification of all sinuses. Prior surgery patients had a mean number of 2.0 prior surgeries, and SCS use patients had 1.6 SCS courses in the previous 2 years.

dHigher scores indicate greater disease severity.

AM, morning; Q4W, once every 4 weeks.

References:

  1. DUPIXENT Prescribing Information.
  2. Data on file, Sanofi US. Clinical overview (chronic rhinosinusitis with nasal polyposis). 2018.
  3. Data on file, Sanofi US. LIBERTY NP SINUS-52, CSR. 2018.
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 versus 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 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%) in patients are injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye, and eosinophilia. The safety profile in pediatric patients 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 ± TCS in pediatric patients observed through Week 52 was consistent with that seen in adults with atopic dermatitis, with hand-foot-and-mouth disease and skin papilloma (incidence ≥2%) reported in patients 6 months to 5 years of age. These cases did not lead to study drug discontinuation.
  • 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.
  • Eosinophilic esophagitis: The most common adverse reactions (incidence ≥2%) are injection site reactions, upper respiratory tract infections, arthralgia, and herpes viral infections.

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

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 months 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.

Eosinophilic Esophagitis: DUPIXENT is indicated for the treatment of adult and pediatric patients aged 12 years and older, weighing at least 40 kg, with eosinophilic esophagitis (EoE).