Date: 16-Sep-2020

US FDA Grants Breakthrough Therapy Status To Dupixent To Treat Eosinophilic Esophagitis

Regeneron Pharmaceuticals Inc and Sanofi announced the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Dupixent (dupilumab) for the treatment of patients 12 years and older with eosinophilic esophagitis (EoE). The designation for this investigational use is based on positive results from Part A of a phase 3 trial in patients with EoE.

There are currently no US FDA-approved medicines for EoE, a chronic and progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly. Over time, excessive type 2 inflammation causes scarring and narrowing of the esophagus, making it difficult to swallow. If left untreated, EoE can affect a patient's ability to eat and cause food to become stuck after being swallowed (food impaction), which can lead to a medical emergency. In the US alone, there are approximately 160,000 patients with EoE who are currently being treated with various unapproved therapies or diet modification. Of these patients, approximately 50,000 have failed multiple treatments.

Regeneron and Sanofi previously reported positive results from Part A of the pivotal phase 3 trial evaluating Dupixent in patients 12 years and older with EoE. Part A of the randomized, double-blind, placebo-controlled trial of 81 patients met both of its co-primary endpoints, as well as all key secondary endpoints. Patients treated weekly with Dupixent 300 mg over a 24-week treatment period experienced a reduction in symptoms, esophageal inflammation and abnormal endoscopic findings in the esophagus. The trial demonstrated safety results consistent with the known safety profile of Dupixent in its approved indications. The EoE 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) after completing either Part A or Part B.

In 2017, Dupixent also was granted Orphan Drug Designation for the potential treatment of EoE. This is given to investigational medicines intended for the treatment of rare diseases that affect fewer than 200,000 people in the US.

The potential use of Dupixent in eosinophilic esophagitis is currently under clinical development, and its safety and efficacy for this indication have not been evaluated by any regulatory authority.

Dupixent is approved in the US to treat patients aged 6 years and older with moderate-to-severe atopic dermatitis that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies; for use with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in patients aged 12 years and older whose asthma is not controlled with their current asthma medicines; and for use with other medicines for the maintenance treatment of CRSwNP in adults whose disease is not controlled.

In adolescents 12 years of age or older, it is recommended that Dupixent be administered by or under the supervision of an adult. In children younger than 12 years of age, Dupixent should be administered by a caregiver.

Outside of the US, Dupixent is approved for specific patients with moderate-to-severe atopic dermatitis and certain patients with asthma in a number of other countries around the world, including the EU and Japan. Dupixent is also approved in the EU and Japan to treat certain adults with severe CRSwNP.

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 asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP) and atopic dermatitis.

Dupixent was invented using Regeneron'sVelocImmune 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 to create REGN-COV2, a potentially preventative and therapeutic medicine for COVID-19.

To date, dupilumab has been studied in more than 10,000 patients across 50 clinical trials in various chronic diseases driven by type 2 inflammation. Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.