Site icon pharmaceutical daily

Sanofi, Regeneron: first and only Phase 3 trial in children with EoE shows positive results

This image provided by Sanofi shows a box containing two single-dose pre-filled syringes of the drug Dupixent. On Tuesday, March 28, 2017, the Food and Drug Administration approved Dupixent for moderate or severe eczema, which causes red, fiercely itchy rashes on the face, arms and legs. (Rodrigo Cid/Sanofi via AP)

Dupixent presented detailed data at this year’s UEG Week conference in Vienna from from an investigational Phase 3 trial showing positive results in children ages 1 to 11 years old who are living with eosinophilic esophagitis (EoE). EoE is a chronic, progressive inflammatory disease that damages the esophagus and prevents it from working properly. Of the approximately 21,000 children under the age of 12 in the U.S. currently being treated for EoE, approximately 9,000 are most in need of new treatment options.

Late-breaking positive results from a Phase 3 trial evaluating the investigational use of Dupixent® (dupilumab) in children aged 1 to 11 years with active eosinophilic esophagitis (EoE) will be presented today at United European Gastroenterology (UEG) Week 2022. The data will be submitted to regulatory authorities around the world, starting with the U.S. Food and Drug Administration (FDA) in 2023. In May 2022, Dupixent 300 mg weekly was approved by the FDA to treat EoE in people aged 12 years and older, weighing at least 40 kg.

Mirna Chehade, M.D, from Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine, Mount Sinai, said:
“Eosinophilic esophagitis impacts a child’s fundamental ability to eat, which is especially critical in early childhood when healthy weight gain is vital to long-term health and development. These Phase 3 data support the potential of dupilumab to reduce esophageal damage – caused in part by underlying type 2 inflammation – and showed histological disease remission and signs of weight gain impacting the growth percentile for those children on higher dose Dupixent.”

Dupixent led to significant improvements in the primary efficacy measure for higher (n=37) and lower (n=31) dose groups at 16 weeks in the randomized, placebo-controlled Phase 3 trial. Among children treated with Dupixent, 68% of children on higher dose and 58% of patients on lower dose achieved the primary endpoint of significant histological disease remission, compared to 3% for placebo (both p<0.0001). Children on the higher dose regimen also experienced significant improvements in abnormal endoscopic findings of their esophagus, with a reduction of 3.5 points compared to an increase of 0.3 points for placebo (p<0.0001). Symptomatically, higher dose Dupixent led to a numerical improvement in the proportion of days children experienced disease symptoms from baseline as reported by their caregivers compared to placebo, though not statistically significant. Additionally, a prespecified exploratory analysis was presented which found higher dose Dupixent led to a 3.09 percentile increase in body weight for age percentile from baseline, compared to 0.29 for placebo.

Safety results were generally consistent with the known safety profile of Dupixent in its approved EoE indication for children and adults aged 12 years and older who weigh at least 40 kg. For the 16-week treatment period, the overall rates of adverse events (AEs) were 79% (higher dose n=27/37, lower dose n=26/30) for Dupixent and 91% (n=31/34) for placebo. AEs most commonly observed with Dupixent (≥5%) compared to placebo included COVID-19 (higher dose n=5/37, lower dose n=9/30, placebo n=0/34; all cases were mild or moderate and did not lead to study discontinuation), rash (higher dose n=3/37, lower dose n=3/30, placebo n=2/34), headache (higher dose n=1/37, lower dose n=4/30, placebo n=1/34), viral gastroenteritis (higher dose n=4/37, lower dose n=0/30, placebo n=1/34), diarrhea (higher dose n=2/37, lower dose n=2/30, placebo n=1/34) and nausea (higher dose n=1/37, lower dose n=3/30, placebo n=0/34). Rates of treatment discontinuation due to AEs prior to week 16 were 0% (higher dose n=0/37, lower dose n=0/30) for Dupixent and 6% (n=2/34) for placebo.

The potential use of Dupixent in children with EoE aged 1 to 11 years is currently under clinical development, and the safety and efficacy have not been evaluated by any regulatory authority.

About Eosinophilic Esophagitis

EoE is a chronic inflammatory disease that damages the esophagus and prevents it from working properly. The results seen with Dupixent in adults and children with EoE demonstrate that IL-4 and IL-13 are key and central drivers of the type 2 inflammation underlying this disease.

In children, common symptoms of EoE include acid reflux, vomiting, abdominal discomfort, trouble swallowing, and a failure to thrive. These symptoms can impact growth, weight gain and development, and can cause food-related fear and anxiety which can persist through adulthood. Diet adjustments, which oftentimes include the elimination of many foods, is the standard treatment for EoE, as well as the use of treatments not approved for the disease in children. These include proton pump inhibitors, swallowed topical corticosteroids, or in severe cases, a feeding tube, which may be used to ensure proper caloric intake and weight gain.

Of the approximately 21,000 children under the age of 12 in the U.S. currently being treated for EoE, about 9,000 do not satisfactorily respond to their current treatment regimen and potentially require advanced therapy.


(image: illustration, dupixent)

Exit mobile version