Sanofi/Regenerative Dupixent's Phase III Clinical Treatment For Eosinophilic Esophagitis Has Been Successful!

- Jun 05, 2020-

Sanofi and its partner Regeneron recently announced the evaluation of a new phase anti-inflammatory drug Dupixent (dupilumab) for patients with ≥12 years of age with EosEositis (EoE) critical phase III trial A has achieved positive results . The trial reached two common primary endpoints and all key secondary endpoints.

According to the study, Dupixent is the first and only biological agent to show positive and clinically meaningful results in EoE patients in the ≥12-year-old age group in a phase III clinical trial. Part B of this ongoing phase III trial is evaluating an additional dosing regimen for Dupixent.

EoE is a chronic, progressive type 2 inflammatory disease that damages the esophagus and prevents the esophagus from working properly, causing difficulty swallowing. If left untreated, symptoms and inflammation may develop, leading to impaired esophageal function and scarring. EoE can cause food embolism in the esophagus and requires immediate medical attention. In this phase III trial, almost half of the patients had surgery such as dilated esophagus, and almost three-quarters of patients had received corticosteroid treatment. In the United States, currently about 160,000 EoE patients are receiving treatment, of which about 50,000 patients have failed multiple treatments. At present, in terms of EoE, there is no treatment approved by the US FDA.

The phase III trial announced this time is a randomized, double-blind, placebo-controlled trial that is evaluating the efficacy and safety of Dupixent in the treatment of EoE adolescents and adults. Part A of the trial enrolled 81 EoE patients ≥12 years of age. These patients were confirmed by histology and patient report results. In the study, patients were randomly assigned to receive a weekly subcutaneous injection of 300 mg of Dupixent (n=) or placebo (n=39) for 24 weeks. The common primary endpoints were: change from baseline in the dysphagia symptom questionnaire (DSQ, a measurement tool for dysphagia reported by patients) at week 24, peak intraepithelial eosinophil count ≤6 eosinophils/high power Proportion of patients with visual field (eos/hpf, esophageal inflammation measurement tool). In Part A patients, the baseline DSQ score was 34, and the average baseline eosinophil peak level was 89 eos/hpf.

The results showed that from baseline to the 24th week of treatment: (1) 69% reduction in disease symptoms in the Dupixent group and 32% reduction in the placebo group (p=0.0002). The disease symptoms were measured by the DSQ scale, which is a common major factor in the study End point: On the 0-84 scale, the Dupixent treatment group improved 21.92 points and the placebo group improved 9.60 points. (2) In the Dupixent treatment group, 60% of patients had an eosinophil count drop to the normal range, and 5% in the placebo group, which was another common primary endpoint of the study. (3) Endoscopic abnormal results in the Dupixent group were reduced by 39%, and the placebo group was reduced by 0.6%. This was measured by the endoscopic reference score (EoE-EREFS). The Dupixent group was reduced by 3.2 points and the placebo group was reduced by 0.3 points p <0.0001).

Tests have shown that Dupixent's safety results are similar to the safety profiles known in approved indications. During the 24-week treatment period, the overall adverse event rates for Dupixent and placebo were 86% and 82%, respectively. More common adverse events with Dupixent treatment included injection site reactions (15 in the Dupixent group and 12 in the placebo group) and upper respiratory tract infections (11 in the Dupixent group and 6 in the placebo group). One patient in the Dupixent group discontinued medication due to arthralgia.

Detailed results from the trial will be announced at an upcoming medical conference. In the United States, the FDA granted Dupixent Orphan Drug Designation (ODD) for EoE in 2017.

Dr. George D. Yancopoulos, co-founder, president and chief scientific officer of Regeneron, said: "Eosinophilic esophagitis (EoE) is a debilitating disease and there are currently no approved treatment options. The disease will affect patients The ability to eat, causing severe pain, often leads to repeated emergency room visits and medical procedures. These data are particularly impressive because Dupixent not only significantly reduces eosinophils in the esophagus, but also improves all clinical aspects of the disease , Anatomical and histological indicators. In the past, EoE was considered a disease caused by eosinophils, but other biological agents that reduce esophageal eosinophils have not shown consistent clinical or anatomical improvements. These Dupixent results show that EoE is caused by multiple aspects of type 2 inflammation driven by IL-4 and IL-13. According to this phase III trial, EoE is the fourth atopy or key feature of Dupixent’s key trial data with significant efficacy Type 2 inflammatory disease."

John Reed, MD, Sanofi’s global head of research and development, said: “These data show that Dupixent has the potential to continue to fill the treatment gap of the type 2 inflammatory disease spectrum, including common asthma and rare eosinophilic esophagitis. This phase III trial For the first time, patients report improved swallowing capacity. In some cases, patients with dietary eosinophilic esophagitis require repeated hospital interventions, and these findings are very encouraging."

Dupixent targets a key driver of type 2 inflammation. The drug is a fully humanized monoclonal antibody that specifically inhibits the over-activation signals of two key proteins, IL-4 and IL-13. IL-4/IL-13 are two inflammatory factors and are considered to be key drivers of intrinsic inflammation in allergic diseases and other type 2 inflammatory diseases, including atopic dermatitis, asthma, eosinophilic esophagitis, grass allergy , Peanut allergy, etc.

Dupixent was launched at the end of March 2017 as the world's first biological agent for the treatment of moderate to severe atopic dermatitis. So far, the drug has been approved by many countries and regions, including the United States, the European Union and Japan. In the United States, Dupixent is now approved to treat three types of diseases caused by type 2 inflammation: moderate to severe atopic dermatitis (≥12 year old patients), moderate to severe asthma (≥12 year old patients), and chronicity with nasal polyps Rhinosinusitis (CRSwNP, adult patient).

Currently, Sanofi and Regener are also conducting an extensive clinical project to evaluate Dupixent for the treatment of diseases caused by allergies and other type 2 inflammations, including: childhood asthma (6-11 years old, stage III), childhood atopy Dermatitis (6 months to 5 years, stage II/III), eosinophilic esophagitis (stage III), chronic obstructive pulmonary disease (stage III), bullous pemphigoid (stage III), nodular prurigo ( Stage III), chronic spontaneous urticaria (stage III), food and environmental allergies (stage II).

Dupixent is another important product jointly developed by Sanofi and Regener following the PCSK9 inhibitor lipid-lowering drug Praluent, and is expected to become a game-changing drug. At present, the indication of Dupixent is steadily increasing. The well-known pharmaceutical market research organization EvaluatePharma has predicted that the global sales of the drug in 2024 may reach 8 billion US dollars.