Regeneron and Sanofi today reported progress toward adding new food allergy indications for their marketed drug Dupixent® (dupilumab) with announcements of successful Phase II results in adults with active moderate-to-severe eosinophilic esophagitis, and the launch of a Phase II study with Aimmune Therapeutics assessing the treatment in peanut-allergic patients.
At the World Congress of Gastroenterology (WCOG), held in partnership with The American College of Gastroenterology Annual Scientific Meeting (ACG 2017) in Orlando, FL, Regeneron and Sanofi presented positive results showing that patients who received dupilumab weekly reported a significant improvement in the ability to swallow versus placebo.
In the 12-week Phase II eosinophilic esophagitis study, 47 patients were randomized into two treatment groups, both of which had a mean baseline SDI score of 6.4. Patients received either Dupixent 300 mg weekly following a 600-mg loading dose or placebo. At week 10, patients who received Dupixent 300 mg weekly showed a 45% improvement, namely a three-point reduction in their SDI score, compared to a 19% (1.3 points) improvement for patients randomized to placebo.
Secondary endpoints of the study included measures of the impact of Dupixent on endoscopic and histopathologic measures of disease severity, as well as symptoms. According to Regeneron and Sanofi, the mean change in the Eosinophilic Esophagitis Endoscopic Reference Score (EoE-EREFS) was significantly reduced by 1.9 points from baseline—a 48% improvement—in patients who received Dupixent weekly compared to 0.3 points (7% improvement) for placebo patients at 12 weeks.
EoE-EREFS is a visual measure of disease severity (inflammation and fibrosis in the esophagus) using a scale of 0 to 8; the higher the number, the more severe the disease.
Regeneron and Sanofi said the mean percent change in overall peak intraepithelial eosinophil count from baseline to 12 weeks was reduced by 93% from baseline in patients who received Dupixent weekly, compared to a 14% increase among patients randomized to placebo.
When measured by Eosinophilic Esophagitis Symptom Activity Index (EEsAI), the mean percent change in a composite measure of symptoms and quality of life was numerically improved—though not statistically significant—by 35% in Dupixent patients, and by 11% in patients receiving placebo at 10 weeks.
“Dupilumab, a monoclonal antibody targeting interleukin (IL)-4 and IL-13, significantly improved patients' ability to swallow, inflammation of the esophagus, and endoscopic signs of the disease. These positive Phase II results support further clinical development of dupilumab for patients with eosinophilic esophagitis,” Ikuo Hirano, M.D., professor of medicine, Northwestern University Feinberg School of Medicine, said in a statement.
Launching Combo Therapy Study with Aimmune
Also today, Regeneron and Sanofi agreed to partner with Aimmune in a Phase II trial assessing the combination of Aimmune’s AR101 with adjunctive Dupixent in patients with peanut allergy.
Regeneron agreed to sponsor the trial, Aimmune said, adding that it will provide food challenge materials as well as clinical supply of AR101, a human monoclonal antibody indicated for desensitizing patients with peanut allergy. The biologic oral immunotherapy is designed to inhibit signaling of IL-4 and IL-13 cytokines, which are believed to be major drivers of type 2 inflammation.
The collaboration comes a year and a half after Aimmune reported positive results from the open-label Phase II ARC002 study: All patients who completed 12 weeks of low-dose maintenance therapy were desensitized to levels of peanut protein beyond the 250 to 300 mg typically found in one peanut kernel.
In ARC002, 40 patients completed 12 weeks of post–up-dosing maintenance therapy at a daily dose of 300 mg of AR101. Those patients were then administered a double-blind, placebo-controlled food challenge, in which 100% tolerated cumulative amounts of peanut protein of 443 mg—while 90% tolerated 1043 mg in peanut protein, and 60%, 2043 mg. The results corresponded to 85%, 77%, and 51% on an intent-to-treat basis.
Patients who passed the highest challenge level demonstrated protection against a challenge equivalent to seven or eight peanuts, Aimmune said in March 2016.
“Our Phase II findings showed AR101 was associated with both clinically meaningful levels of desensitization and potential immunomodulatory effects on the immunoglobulin (IgE)–IgG4 ratio and peanut-specific TH2 cells. We look forward to building on these findings and the upcoming readout of our pivotal Phase III PALISADE trial through this clinical collaboration,” Aimmune CEO Stephen Dilly, M.B.B.S., Ph.D., said in a statement.
Last November, Nestlé Health Science announced a $145 million equity investment in Aimmune under a partnership by the companies to develop food allergy immunotherapies.