Date: 2018-09-15
Type of
information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 27th European Academy of Dermatology and Venereology (EADV) Congress
Company: Sanofi (France) Regeneron Pharmaceuticals (USA - NY)
Product: dupilumab
Action
mechanism:
- monoclonal antibody. Dupilumab is a fully-human monoclonal antibody directed against the IL-4 receptor alpha subunit, which blocks signaling from both IL-4 and IL-13. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of the Th2 (Type 2 helper T-cell) immune response, which is believed to be a critical pathway in allergic inflammation. Dupilumab was created using Regeneron's pioneering VelocImmune® technology and is being co-developed with Sanofi in atopic dermatitis, asthma and chronic sinusitis with nasal polyps.
Disease: moderate-to-severe atopic dermatitis
Therapeutic
area: Autoimmune diseases - Dermatological diseases
Country:
Trial
details:
Latest
news:
- • On September 15, 2018, Sanofi and Regeneron Pharmaceuticals announced that detailed results from a pivotal Phase 3 trial showed Dupixent® (dupilumab) monotherapy demonstrated a significant improvement in signs and symptoms of atopic dermatitis and certain quality of life measures in adolescent patients (12-17 years) with moderate-to-severe atopic dermatitis, whose disease was inadequately controlled with topical therapies or for whom topical treatment was medically inadvisable. These data were presented at the 27th European Academy of Dermatology and Venereology (EADV) Congress in Paris, France.
- There continues to be a significant unmet need for adolescents with moderate-to-severe atopic dermatitis, whose disease cannot be controlled with topical treatments. There are no systemic biologic medications approved for this patient population. Dupixent® is currently approved for use in certain adult patients with moderate-to-severe atopic dermatitis in countries including the U.S., European Union, Canada and Japan. The results from this trial in adolescents form the basis of regulatory submissions for patients ages 12 to 17.
- The late-breaking presentation at EADV included the following data:
- The co-primary endpoint outside of the U.S. was 75% improvement in Eczema Area and Severity Index (EASI-75) at 16 weeks. In the U.S., the primary endpoint was the proportion of patients achieving Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear):
- 41.5% of patients who received Dupixent every two weeks and 38% of patients who received Dupixent every four weeks achieved 75% or greater skin improvement (EASI-75) compared to 8% with placebo (p less than 0.001).
- 24% of patients who received weight-based dosing of Dupixent every two weeks (200 mg or 300 mg) and 18% of patients who received a fixed dose of Dupixent every four weeks (300 mg) achieved the primary endpoint – clear or almost-clear skin (IGA; score of 0 or 1) – compared with 2% with placebo (p less than 0.001).
- There was a 66% improvement in the Dupixent every two weeks group and 65% improvement in the Dupixent every four weeks group in average percent change from baseline in EASI score compared with a 24% improvement in the placebo group (p less than 0.001).
- There was a 48% improvement in the Dupixent every two weeks group and 45.5% improvement in the Dupixent every four weeks group in average percent change from baseline in the pruritus numerical rating scale (NRS) compared with a 19% improvement in the placebo group (p less than 0.001).
- Also at 16 weeks, additional secondary endpoints were:
- The majority of patients who received Dupixent (61% of patients treated every two weeks and 55% of patients treated every four weeks) achieved at least a 50% improvement in EASI (EASI-50) compared to 13% with placebo (p less than 0.001).
- There was a 52% improvement in the Dupixent every two weeks group and 47.5% improvement in the Dupixent every four weeks group compared to a 18% improvement in the placebo group in mean percent change from baseline in SCORing Atopic Dermatitis (SCORAD), a combined measure of area and severity of atopic dermatitis on the skin as well as patient-reported symptoms of itch and sleeplessness (p less than 0.001).
- Itch – 49% of patients who received Dupixent every two weeks and 39% of patients who received Dupixent every four weeks achieved at least a 3-point improvement on the peak pruritus numerical rating scale (pp-NRS) compared to 9% with placebo (p less than 0.001). At the beginning of the trial, patients reported a mean itch score of 7.6 on the 10-point pp-NRS scale.
- Quality of Life and Patient-Reported Symptoms – Patients who received Dupixent every two weeks or every four weeks significantly improved quality of life measured by the Children’s Dermatology Life Quality Index (CDLQI) and patient-reported symptoms measured by the Patient-Oriented Eczema Measure (POEM) compared with placebo (p less than 0.001).
- Additionally in the 16-week trial, 59% of patients on placebo used rescue medications compared with 21% of patients receiving Dupixent every two weeks and 32.5% of patients receiving Dupixent every four weeks.
- The overall rate of adverse events was 72% for Dupixent every two weeks, 64% for Dupixent every four weeks and 69% for placebo. Adverse events that were observed more frequently with Dupixent included injection site reactions (8.5% for Dupixent every two weeks, 6% for Dupixent every four weeks compared with 3.5% for placebo) and conjunctivitis (10% for Dupixent every two weeks, 11% for Dupixent every four weeks compared with 5% for placebo). Skin infections were numerically lower in the Dupixent groups (11% for Dupixent every two weeks, 13% for Dupixent every four weeks compared with 20% for placebo).
Is
general: Yes
