SAN ANTONIO — A new option for eosinophilic esophagitis met its primary and key secondary end points in the pivotal phase 3 ORBIT study, the largest trial to date in a therapeutic area with limited treatment choices.
Findings from the induction-phase trial of budesonide oral suspension (Takeda) were presented here at the American College of Gastroenterology (ACG) 2019 Annual Scientific Meeting.
"This is the first phase 3 trial to demonstrate symptom efficacy using the validated Dysphagia Symptom Questionnaire," said Ikuo Hirano, MD, from the Northwestern University Feinberg School of Medicine in Chicago.
The two primary end points of the study were histologic response and dysphagia relief after 12 weeks of therapy. Of the 318 adolescents and adults — aged 11 to 55 years — participating in the study, 213 were randomly assigned to budesonide oral suspension 2 mg and 105 were assigned to placebo twice a day.
There were more histologic and dysphagia symptom responders in the budesonide group than in the placebo group.
|Table. Rates of Response|
|Response||Budesonide Group, %||Placebo Group, %||P Value|
The key secondary end point — improvement in average score on the patient-reported Dysphagia Symptom Questionnaire (DSQ) — was significantly better in the budesonide group than in the placebo group (−13.0 vs −9.1; P = .015).
Adverse effects were mostly mild or moderate, were similar in the two groups, and were all deemed to be unrelated to the treatment, Hirano reported.
The trial received funding from Takeda, maker of the budesonide oral suspension. Hirano's medical center has received research support from Shire, which is owned by Takeda, and some of his fellow investigators are consultants for Shire.
"We've been doing this off-label for a while," said ACG President Sunanda Kane, MD, from the Mayo Clinic in Rochester, Minnesota.
"When you go to talks about eosinophilic esophagitis, the first-line therapy is usually acid suppression. But patients either don't have an adequate response or they're afraid of acid suppression because of the bad press that proton pump inhibitors [PPIs] have received," she explained.
And although PPIs work for some patients, "it's only going to be okay. It's not going to be a panacea, and it's certainly not going to be what you can use for everybody," she added.
ORBIT shows that "not only are you getting rid of symptoms, you're improving quality of life and you're healing the esophagus," said Kane. "It's a threefold win here."
The results represent a "breakthrough" because they are not anecdotal findings from a series of cases; they come from a placebo-controlled, double-blind, multisite trial that involved a large number of patients, she pointed out.
Esophagitis is "yet another autoimmune inflammatory disorder — like lupus, like asthma, like inflammatory bowel disease — that we are seeing increased rates of," she said.
Some patients have been treated with elimination diets, but that is onerous because typically the foods that trigger the disease are milk and wheat, said Hirano.
Topical corticosteroids designed to treat asthma are also used, but patients have to squirt the spray into their mouths and gulp down the vapor to coat the esophagus, he told Medscape Medical News.
But medications not designed to be delivered to the esophagus can cause problems, and there can be reimbursement roadblocks associated with off-label use.
The budesonide oral suspension is a premixed solution with enough viscosity that it sticks to the esophagus.
Hirano said that in his own practice, he discusses all the options for treatment with his patients. Budesonide appears to work in a majority, but not all, patients, he added.
Some patients with eosinophilic esophagitis have symptoms weekly or daily, and some experience severe food impaction, an extreme form of dysphagia in which food — typically a chunk of meat — gets caught in the esophagus and can lead to a visit to the emergency department, he explained.
"I have patients who would always sit near a bathroom at a restaurant because they didn't want the embarrassment of vomiting in the course of a public meal," he said. "That's the hope of getting a medication like this approved."
A 36-week maintenance-phase extension — ORBIT2 — is currently ongoing.
American College of Gastroenterology (ACG) 2019 Annual Scientific Meeting Presidential plenary session 1. Presented October 28, 2019.
Medscape Medical News © 2019
Cite this: New Treatment Option Emerging for Esophagitis - Medscape - Oct 31, 2019.