- Dupixent 300 mg weekly is the only biologic medicine to show positive, clinically meaningful Phase 3 results in adults and adolescents with eosinophilic esophagitis
- Data continue to support well-established safety profile of Dupixent
- U.S. and global regulatory filings are planned in 2022
PARIS, France and TARRYTOWN, NY, USA I February 26, 2022 I Positive detailed results from a second Phase 3 trial showed that Dupixent® (dupilumab) 300 mg weekly significantly improved the signs and symptoms of eosinophilic esophagitis (EoE) at 24 weeks compared to placebo in patients 12 years and older. Eosinophilic esophagitis is a chronic, progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly. These pivotal data will be presented today at the 2022 American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting during a late-breaking oral abstract session.
Evan S. Dellon
M.D., M.P.H., Professor of Gastroenterology and Hepatology at the University of North Carolina School of Medicine and co-principal investigator of the trial
“Eosinophilic esophagitis can greatly impact a person’s ability to eat normally, and physicians have to rely on invasive medical procedures to monitor and, in more serious cases, stretch the esophagus. Currently, there are no FDA-approved treatment options that address the underlying drivers of this disease. The data from this trial showed dupilumab taken weekly not only improved patients’ ability to swallow, but also reduced markers of type 2 inflammation in the esophagus, indicating its potential to address a major underlying cause of eosinophilic esophagitis.”
Topline results from the Dupixent 300 mg weekly arm of the trial, which enrolled 80 patients in the Dupixent group and 79 patients in the placebo group, were announced in October 2021 and confirm results from the first Phase 3 trial. The co-primary endpoints at 24 weeks assessed patient-reported measures of difficulty swallowing (change from baseline in the 0-84 Dysphagia Symptom Questionnaire, or DSQ), and esophageal inflammation (proportion of patients achieving histological disease remission, defined as peak esophageal intraepithelial eosinophil count of ≤6 eos/high power field [hpf]).
Data presented at the 2022 AAAAI Annual Meeting showed that patients treated with Dupixent 300 mg weekly experienced the following changes by week 24 compared to placebo:
- 64% reduction in disease symptoms from baseline compared to 41% for placebo (p=0.0008). Patients receiving Dupixent experienced a 23.78 point improvement on the DSQ, compared to a 13.86 point improvement for placebo (p<0.0001); baseline DSQ scores were approximately 38 and 36 points, respectively.
- Nearly 10 times as many patients receiving Dupixent achieved histological disease remission: 59% of patients achieved histological disease remission compared to 6% of patients receiving placebo (p<0.0001); mean baseline peak levels were 89 and 84 eos/hpf, respectively.
The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved indications. For the 24-week treatment period (Dupixent n=80, placebo n=78), overall rates of adverse events were 84% for Dupixent 300 mg weekly and 71% for placebo. Adverse events that were more commonly (≥5%) observed with Dupixent every week included injection site reactions (38% Dupixent, 33% placebo), fever (6% Dupixent, 1% placebo), sinusitis (5% Dupixent, 0% placebo), COVID-19 (5% Dupixent, 0% placebo) and hypertension (5% Dupixent, 1% placebo). No imbalance was observed in rates of treatment discontinuation due to adverse events between Dupixent (3%) and placebo (3%) groups prior to week 24.
The trial also found that significantly more patients treated with Dupixent 300 mg every two weeks reduced their esophageal eosinophilic count to the normal range compared to placebo; however there was not a significant improvement in dysphagia symptoms. Detailed results on the every two week dosing will be presented at an upcoming congress.
Data from the clinical trial program have been submitted to the U.S. Food and Drug Administration (FDA). Global regulatory filings in other countries are also planned in 2022.
In September 2020, the U.S. FDA granted Breakthrough Therapy designation to Dupixent for the treatment of patients 12 years and older with EoE. Dupixent was also granted Orphan Drug designation for the potential treatment of EoE in 2017. The potential use of Dupixent in EoE is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority.
About Eosinophilic Esophagitis (EoE)
EoE is a chronic, progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly. For patients with EoE, swallowing the smallest amount of food or taking a sip of water can be a painful and worrisome choking experience. This disease can also cause narrowing of the esophagus and dilation (physical expansion) of the esophagus may be needed, which is often painful. In severe cases, a feeding tube is the only option to ensure proper caloric intake and weight gain. There are approximately 160,000 patients in the U.S. living with EoE who are currently treated, of whom approximately 48,000 have failed multiple treatments.
About the Dupixent Eosinophilic Esophagitis Trial
The Phase 3 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent in adolescents and adults with EoE. This second trial (Part B) enrolled 240 patients aged 12 years and older with EoE, as determined by histological and patient-reported measures. Following the first Phase 3 trial (Part A), in which Dupixent 300 mg weekly was evaluated compared to placebo, the second confirmatory trial evaluated Dupixent 300 mg weekly or every two weeks compared to placebo for a 24-week treatment period.
The clinical trial program is ongoing, with patients from the first and second trials continuing into a 28-week long-term extension trial (Part C). Full results from this trial will be available later this year.
About Dupixent
Dupixent is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP).
Dupixent is currently approved in the U.S., Europe, Japan and other countries around the world for use in specific patients with moderate-to-severe atopic dermatitis, as well as certain patients with asthma or CRSwNP in different age populations. Dupixent is also approved in one or more of these indications in more than 60 countries around the world and more than 350,000 patients have been treated globally.
Dupilumab Development Program
Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement. To date, dupilumab has been studied across 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
In addition to the currently approved indications, Sanofi and Regeneron are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes, including eosinophilic esophagitis (Phase 3), pediatric atopic dermatitis (6 months to 5 years of age, Phase 3), chronic rhinosinusitis without nasal polyposis (Phase 3), chronic obstructive pulmonary disease with evidence of type 2 inflammation (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), bullous pemphigoid (Phase 3), chronic inducible urticaria-cold (Phase 3), allergic fungal rhinosinusitis (Phase 3), allergic bronchopulmonary aspergillosis (Phase 3) and peanut allergy (Phase 2). These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
SOURCE: Regeneron Pharmaceuticals
