Dupixent® (dupilumab) Eosinophilic Esophagitis Trial Meets Both Co-Primary Endpoints
Dupixent demonstrated significant clinical and anatomic improvements, including the ability to swallow, in Part A of pivotal trial
69% reduction in disease symptoms with Dupixent, compared to 32% for placebo (p=0.0002)
There are currently no FDA-approved treatments for eosinophilic esophagitis, a condition that impacts patients' ability to eat
EoE is a chronic and progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly, leading to difficulties in swallowing. If untreated, symptoms and inflammation can progress, causing functional damage and scarring of the esophagus. EoE can lead to esophageal food impaction, requiring immediate emergency room visits. Almost half of the patients in this trial had prior procedures such as dilation of their esophagus, and almost three-quarters had previously been treated with corticosteroids. In the
"Eosinophilic esophagitis can be debilitating, and there are no approved treatment options. It impacts patients' ability to eat, causes severe pain and often results in repeated emergency room visits and medical procedures," said
"These data demonstrate Dupixent's potential to continue to address treatment gaps across the spectrum of type 2 inflammatory diseases as common as asthma and as rare as eosinophilic esophagitis," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "For the first time in a Phase 3 trial, patients reported an improvement in their ability to swallow food. For patients with eosinophilic esophagitis who are living with restricted diets and, in some cases, repeated hospital interventions, these findings are encouraging."
Part A of the trial enrolled 81 patients (42 with Dupixent, 39 with placebo) aged 12 years and older with EoE, as determined by histological and patient-reported measures. The co-primary endpoints assessed the change from baseline in the Dysphagia Symptom Questionnaire (DSQ), a patient-reported measure of difficulty swallowing, and the proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf, a measure of esophageal inflammation, at 24 weeks.
Patients treated with Dupixent 300 mg weekly experienced the following changes by week 24 from baseline:
- 69% reduction in disease symptoms compared to 32% for placebo (p=0.0002). Disease symptoms were measured by the DSQ scale, where patients experienced a 21.92 point improvement with Dupixent compared to a 9.60 point improvement for placebo, on a 0-84 scale (p=0.0004), the co-primary endpoint; baseline DSQ scores were approximately 34 points.
- 60% reduction in their esophageal eosinophilic count to a normal range compared to 5% for placebo (p<0.0001), the co-primary endpoint. This was measured by the proportion of patients who achieved a peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf (a normal range); mean baseline peak levels were 89 eos/hpf.
- 39% reduction in abnormal endoscopic findings compared to 0.6% for placebo. This was measured by the EoE Endoscopic Reference Score (EoE-EREFS), where patients experienced a 3.2 point reduction with Dupixent compared to a 0.3 point reduction for placebo (p<0.0001).
The trial demonstrated similar safety results to the known safety profile of Dupixent in its approved indications. For the 24-week treatment period, overall rates of adverse events were 86% for Dupixent and 82% for placebo. Adverse events that were more commonly observed with Dupixent included injection site reactions (n=15 for Dupixent and n=12 for placebo) and upper respiratory-tract infections (n=11 for Dupixent and n=6 for placebo). There was one treatment discontinuation in the Dupixent group due to arthralgia.
Detailed results from this trial will be presented at an upcoming medical meeting. Dupixent received Orphan Drug Designation from the FDA in 2017 for the potential treatment of EoE. This status is given to investigational medicines intended for the safe and effective treatment of rare diseases that affect fewer than 200,000 people in the
Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. Data from Dupixent clinical trials have shown that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis.
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 eosinophilic esophagitis. Part A of the trial enrolled 81 patients aged 12 years and older with eosinophilic esophagitis, as determined by histological and patient-reported measures. In total, 85% of these patients suffered from at least one concurrent atopic condition such as allergic rhinitis, food allergy and asthma. Patients received weekly subcutaneous injections of Dupixent 300 mg or placebo for the 24-week treatment period.
The trial is ongoing, with additional patients enrolling in Part B as well as patients continuing in a 28-week extended active treatment period (Part C).
Dupilumab Development Program
In addition to the currently approved indications, Regeneron and Sanofi are also studying dupilumab in a broad range of clinical development programs for diseases driven by allergic and other type 2 inflammation, including pediatric asthma (6 to 11 years of age, Phase 3), pediatric atopic dermatitis (6 months to 5 years of age, Phase 2/3), chronic obstructive pulmonary disease (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), and food and environmental allergies (Phase 2). These potential uses are investigational, and the safety and efficacy have not been evaluated by any regulatory authority. Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.
Dupilumab was invented using Regeneron's proprietary VelocImmune® technology that utilizes a proprietary genetically-engineered mouse platform endowed with a genetically-humanized immune system to produce optimized fully-human antibodies. VelocImmune technology has been used to create multiple antibodies including Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab) and Kevzara® (sarilumab), which are approved in multiple countries around the world. Regeneron previously used these technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the FDA, and is now being used in efforts to create prophylactic and treatment medicines for COVID-19.
DUPIXENT is a prescription medicine used:
- to treat people 12 years of age and older 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 with atopic dermatitis under 12 years of age.
- with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in people aged 12 years and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 12 years of age.
- with other medicines to treat chronic rhinosinusitis with nasal polyposis in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.
IMPORTANT SAFETY INFORMATION FOR
Do not use if you are allergic to dupilumab or to any of the ingredients in DUPIXENT®.
Before using DUPIXENT, tell your healthcare provider about all your medical conditions, including if you:
- have eye problems.
- have a parasitic (helminth) infection.
- are taking oral, topical, or inhaled corticosteroid medicines. Do not stop taking your corticosteroid medicines unless instructed by your healthcare provider. This may cause other symptoms that were controlled by the corticosteroid medicine to come back.
- are scheduled to receive any vaccinations. You should not receive a "live vaccine" if you are treated with DUPIXENT.
- are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby.
- are breastfeeding or plan to breastfeed. It is not known whether DUPIXENT passes into your breast milk.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. If you are taking asthma medicines, do not change or stop your asthma medicine without talking to your healthcare provider.
DUPIXENT can cause serious side effects, including:
- Allergic reactions (hypersensitivity), including a severe reaction known as anaphylaxis. Stop using DUPIXENT and tell your healthcare provider or get emergency help right away if you get any of the following symptoms: breathing problems, fever, general ill feeling, swollen lymph nodes, swelling of the face, mouth and tongue, hives, itching, fainting, dizziness, feeling lightheaded (low blood pressure), joint pain, or skin rash.
- Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision.
- Inflammation of your blood vessels. Rarely, this can happen in people with asthma who receive DUPIXENT. This may happen in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. It is not known whether this is caused by DUPIXENT. Tell your healthcare provider right away if you have: rash, shortness of breath, persistent fever, chest pain, or a feeling of pins and needles or numbness of your arms or legs.
The most common side effects include:
- Atopic dermatitis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, and cold sores in your mouth or on your lips.
- Asthma: injection site reactions, pain in the throat (oropharyngeal pain), and high count of a certain white blood cell (eosinophilia).
- Chronic rhinosinusitis with nasal polyposis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, high count of a certain white blood cell (eosinophilia), trouble sleeping (insomnia), toothache, gastritis, and joint pain (arthralgia).
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of DUPIXENT. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Use DUPIXENT exactly as prescribed. DUPIXENT is an injection given under the skin (subcutaneous injection). If your healthcare provider decides that you or a caregiver can give DUPIXENT injections, you or your caregiver should receive training on the right way to prepare and inject DUPIXENT. Do not try to inject DUPIXENT until you have been shown the right way by your healthcare provider. In children 12 years of age and older, it is recommended that DUPIXENT be administered by or under supervision of an adult.
Please see full Prescribing Information including Patient Information.
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.
Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.
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