The European Commission ( EC ) has expanded the marketing authorization for Dupixent ( Dupilumab ) in the European Union ( EU ) to treat eosinophilic esophagitis ( EoE ) in adults and adolescents 12 years and older, weighing at least 40 kg, who are inadequately controlled by, are intolerant to, or who are not candidates for conventional medicinal therapy.
Eosinophilic esophagitis is a chronic, progressive inflammatory disease that damages the esophagus and prevents it from working properly.
With this approval, Dupixent is the first targeted medicine specifically indicated to treat eosinophilic esophagitis in Europe and the U.S.
The EC decision is supported by 52-week data from a phase 3 trial consisting of three parts ( Part A, B and C ).
Part A and Part B have investigated Dupixent 300 mg weekly ( Part A n=42; Part B n=80 ) compared to placebo ( Part A n=39; Part B n=79 ) for 24 weeks.
Part C ( n=188 ) observed patients who had continued on or switched to Dupixent from Parts A and B for an additional 28 weeks.
Dupixent patients in Parts A and B, respectively, have experienced:
- an approximately 10 times higher rate of histological disease remission ( 60% and 59% ), a co-primary endpoint, compared to placebo ( 5% and 6% );
- a 69% and 64% reduction in disease symptoms compared to 32% and 41% with placebo. Disease symptoms were measured using the Dysphagia Symptom Questionnaire ( DSQ ), on which Dupixent patients experienced a 21.9- and 23.8-point clinically meaningful improvement compared to a 9.6- and 13.9-point improvement for placebo, a co-primary endpoint. Swallowing improvement was observed as early as four weeks;
- a greater than seven-fold reduction in abnormal endoscopic findings from baseline ( -3.2 and -4.5 points ) compared to placebo ( -0.3 and -0.6 points );
- nominally significant improvements in swallowing-related pain and health-related quality of life, as well as less frequent non-swallowing symptoms;
- histological disease remission, swallowing improvement and reduction in abnormal endoscopic findings were consistent with the overall population in patients who were uncontrolled, or not-responsive to or not-eligible for swallowed topical corticosteroids. Longer term efficacy in Part C was similar to results observed in Parts A and B.
The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved indications.
The most common side effects across indications include injection site reactions, conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes and eosinophilia.
Adverse events more commonly observed in patients with eosinophilic esophagitis treated with Dupixent ( n=122 ) compared to placebo ( n=117 ) included infections ( 32% vs. 25% ).
An additional adverse reaction of injection site bruising was reported in the eosinophilic esophagitis trial.
The safety profile through 52 weeks was generally consistent with the safety profile observed at 24 weeks.
The three-part phase 3 randomized, double-blind, placebo-controlled trial has evaluated the efficacy and safety of Dupixent in patients aged 12 years and older with eosinophilic esophagitis.
All patients had previously not responded to proton pump inhibitors, and, across Parts A and B, 74% of patients were previously treated with swallowed topical corticosteroids.
At 24 weeks, the co-primary endpoints in Parts A and B assessed patient-reported measures of difficulty swallowing ( change from baseline in the DSQ on a 0-84 scale ) and esophageal inflammation ( proportion of patients achieving histological disease remission, defined as peak esophageal intraepithelial eosinophil count of less than or equal to 6 eos/hpf ).
Additional endpoints included abnormal endoscopic findings ( EoE Endoscopic Reference Score [ EoE-EREFS ] on a 0-18 scale ), swallowing-related pain ( DSQ pain score ), health-related quality of life ( EoE Impact Questionnaire [ EoE-IQ ] ) and frequency of other non-dysphagia symptoms ( EoE Symptom Questionnaire [ EoE-SQ ] ).
Dupixent is an injection administered under the skin ( subcutaneous injection ) at different injection sites.
In the European Union for adolescents and adults with eosinophilic esophagitis, Dupixent is administered at 300 mg every week. It is available as both a pre-filled pen and pre-filled syringe at the 300 mg dose.
Dupixent is intended for use under the guidance of a healthcare professional and can be given in a clinic or at home by self-administration after training by a healthcare professional.
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.
The Dupixent development Program has shown significant clinical benefit and a decrease in type 2 inflammation in phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases.
For people with eosinophilic esophagitis, swallowing even small amounts of food can be a painful and worrisome choking experience. They are often left to contend with the frustration and anxiety of a constantly evolving list of foods to avoid, a poor quality of life and a higher risk of depression.
In cases where eosinophilic esophagitis causes the esophagus to narrow, forced and potentially painful dilation ( physical expansion ) of the esophagus may be needed. In severe cases, a feeding tube may be the only option to ensure proper caloric intake and adequate nutrition.
In the European Union, about 50,000 adults and adolescents live with severe uncontrolled eosinophilic esophagitis. ( Xagena )
Source: Sanofi, 2023