Sanofi: Positive Phase 3 results presented for Dupixent® (dupilumab)
Positive Phase 3 results presented for Dupixent® (dupilumab) show significant improvement on multiple measures of disease severity in adolescents with moderate-to-severe atopic dermatitis
- Results on skin clearing, itch and certain quality of life measurements were presented today as a late-breaking oral presentation at the 27th EADV Congress
Paris and Tarrytown, NY - September 15, 2018 - 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 today 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.
"Limited treatment options leave adolescents with uncontrolled moderate-to-severe atopic dermatitis to cope with intense, unrelenting itch and skin lesions," said Amy S. Paller, M.D., Director of the Northwestern University Skin Disease Research Center and principal investigator of the trial. "The results we are presenting today show the potential for Dupixent in adolescents to not only help clear the skin and reduce itching, but also improve certain aspects of quality of life in adolescents who may be dealing with these unbearable symptoms."
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).
The safety and efficacy of Dupixent in the adolescent atopic dermatitis population have not been fully evaluated by any regulatory authority.
About the Dupixent Trial in Adolescent Patients
The pivotal, Phase 3 trial evaluating the efficacy and safety of Dupixent monotherapy in adolescent patients with moderate-to-severe atopic dermatitis is the first Phase 3 trial of a biologic in this patient population. The trial enrolled 251 patients who were 12 years to 17 years of age with moderate-to-severe atopic dermatitis whose disease could not be adequately controlled with topical medications or for whom topical treatment was medically inadvisable.
Patients were randomized into one of three treatment groups for the controlled period of 16 weeks: the first group was treated with Dupixent subcutaneous injection 200 mg or 300 mg every two weeks, based on weight (with an initial dose of 400 mg or 600 mg respectively). The second group was treated with 300 mg Dupixent every four weeks (with an initial dose of 600 mg), and the third group was treated with placebo every two weeks. No topical corticosteroids were permitted unless a patient had a severe flare and required rescue medication.
The co-primary endpoints outside of the U.S. and a key secondary endpoint in the U.S. was the proportion of patients who achieved 75% or greater skin improvement as measured by the EASI-75 at Week 16. EASI is a validated scale used to measure the extent and severity of the disease. In the U.S., the primary endpoint of this trial was the proportion of patients with an IGA score of 0 or 1 at Week 16. The IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) that measures overall severity of skin lesions.
In the trial, 92% of patients had at least one other atopic or allergic condition, including 66% with allergic rhinitis, 61% with food allergy, 54% with asthma, 29% with hives and 23% with allergic conjunctivitis.
About Moderate-to-Severe Atopic Dermatitis
Atopic dermatitis, a form of eczema, is a chronic inflammatory disease with symptoms often appearing as a rash on the skin.,,, Moderate-to-severe atopic dermatitis is characterized by rashes that can potentially cover much of the body, and can include intense, persistent itching, skin lesions and skin dryness, cracking, redness, crusting and oozing. Itch is one of the most burdensome symptoms for patients and can be debilitating.
About Dupixent® (dupilumab)
Dupixent works by inhibiting interleukin-4 and interleukin-13 (IL-4 and IL-13), which are important contributors to Type 2 inflammation, a systemic, allergic response known to play a role in moderate-to-severe atopic dermatitis.
In 2016, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for Dupixent for the treatment of moderate-to-severe (12 to 17 years of age) and severe (6 months to 11 years of age) atopic dermatitis not well controlled on topical prescription medications.
Dupixent is currently approved in the United States as a treatment for adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupixent is approved in the European Union for use in adults with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy. Dupixent is also approved for certain patients with moderate-to-severe atopic dermatitis in a number of other countries, including Canada and Japan. More than 50,000 adult patients with atopic dermatitis have been prescribed Dupixent to date.
About Type 2 Inflammation in Atopic Dermatitis
Through scientific advances in immune based disease biology, we now understand that a particular type of inflammation, called Type 2 inflammation, contributes to the cause of atopic dermatitis. The immune system includes different immune cells and signaling proteins, including interleukins. Interleukin-4 (IL-4) and interleukin-13 (IL-13) are central drivers of Type 2 allergic inflammation in atopic dermatitis, as well as a range of other allergic or atopic diseases.7
Dupilumab Development Program
Sanofi and Regeneron are also studying dupilumab in a broad range of clinical development programs for diseases driven by Type 2 inflammation, including asthma (Phase 3), pediatric (6-11 years) atopic dermatitis (Phase 3), nasal polyps (Phase 3), eosinophilic esophagitis (Phase 3) and grass allergy (Phase 2). Future trials are planned for chronic obstructive pulmonary disease and food allergy (including peanut). These potential uses are investigational and the safety and efficacy have not been evaluated by any regulatory authority. Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement.
Dupixent is used to treat adult patients with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. Dupixent can be used with or without topical corticosteroids. It is not known if Dupixent is safe and effective in children.
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Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune® which produces optimized fully-human antibodies, and ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
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 Eichenfield et al. Guidelines of Care for Atopic Dermatitis. AAD 2014, pp. 118.
 Guideline to treatment, European Dermatology Forum. http://www.euroderm.org/edf/index.php/edf-guidelines/category/5-guidelines-miscellaneous?download=36:guideline-treatment-of-atopic-eczema-atopic-dermatitis. Accessed December 23, 2016.
 Gelmetti and Wolleberg, BJD 2014, Atopic dermatitis- all you can do from the outside. Page 19.
 National Institutes of Health (NIH). Handout on Health: Atopic Dermatitis (A type of eczema) 2013. http://www.niams.nih.gov/Health_Info/Atopic_Dermatitis/default.asp. Accessed October 31, 2016.
 Mount Sinai. Patient Care Atopic Dermatitis. Available at: http://www.mountsinai.org/patient-care/health-library/diseases-and-conditions/atopic-dermatitis#risk. Accessed August 2017.
 Zuberbier T et al. Patient perspectives on the management of atopic dermatitis. J Allergy Clin Immunol vol. 118, pp. 226-232, 2006.
 Gandhi NA, BL Bennett, NM Graham, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov 2016;15(1):35-50.