A topical formulation of fluticasone designed to dissolve and coat the esophagus appears safe and effective for the treatment of eosinophilic esophagitis (EOE), according to new results from a phase 2b study. The results pave the way for phase 3 clinical trials.
Topical steroids are frequently used off-label for EOE. They may be repurposed from nebulizers used for asthma, with patients mixing the drugs themselves or sending them to a pharmacy to be compounded. Patients remove the spacer from a nebulizer in order to swallow the active compound or mix the liquid that would be nebulized with honey or Splenda to thicken it to maximize its contact with the esophagus. “Both of these things are very cumbersome and difficult. I get a lot of complaints from patients [that] it doesn’t taste good. So, the fact that we have a drug that we are already using, but it’s designed for the esophagus, is really exciting,” said Nielsen Fernandez-Becker, MD, PhD, of the department of gastroenterology and hepatology at Stanford (Calif.) University. Dr. Fernandez-Becker referred some patients to the trial and performed some procedures.
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“I don’t think the findings are unexpected, given what we’ve seen with swallowed inhalers with fluticasone, but I think the real importance of this is that it does look like a dedicated swallow form works. And if this leads to [Food and Drug Administration] approval, then I think that that really becomes a game-changer for this EOE population. Getting something that’s FDA approved to treat this disorder is a key unmet need,” said John Clarke, MD, who was not involved in the study.
He also pointed out that the safety profile of the drug appears good with respect to both candidiasis and adrenal suppression. “It at least seems comparable, if not better than what we’re currently doing with the inhaler,” said Dr. Clarke, a clinical professor of medicine and director of the esophagus program at Stanford University.
Current options for EOE are limited primarily to the use of proton pump inhibitors and food-elimination diets. Oral budesonide is available to patients in Europe and under investigation in the United States.
The new formulation (APT-1011, Ellodi Pharmaceuticals) is meant to be taken without water and dissolves on the tongue and then coats the esophagus.
In the phase 2b study published in Clinical Gastroenterology and Hepatology, researchers randomized 106 adults from six countries with EOE to receive one of four doses of APT-1011, or placebo. Participants had to have current symptoms of dysphagia and active disease after no histologic response from at least 8 weeks of high-dose (20-40 mg/day) proton pump inhibitors. The study included a placebo-controlled, 12-week induction period followed by 40 weeks of maintenance therapy with no placebo arm. The researchers considered a count of fewer than six eosinophils per high-powered field, as measured during an esophageal biopsy, to be a histologic response.
No patients in the placebo group had a response. The response rate was 80% among patients taking a 3-mg dose twice per day; 67% among those taking a 3-mg dose only at bedtime; 86% for those taking 1.5 mg twice per day; and 48% for 1.5 mg only at bedtime (P < .001 for all comparisons to placebo).
After 12 weeks, EOE Endoscopic Reference Score (EREFS) improved from 4.5 to 2.3 in the 3-mg b.i.d. group (5.3-2.1 for bedtime only), and from 4.6 to 1.7 for the 1.5-mg b.i.d. group (5.3-2.9 for 1.5 bedtime only). In the placebo group, the change was from 5.2 to 4.5.
Among those who responded during the induction period, the majority continued to be responders at weeks 26 and 52, including the 3-mg b.i.d. group (88% and 69%, respectively), the 3-mg bedtime-only group (79% and 64%), the 1.5-mg b.i.d. group (89% and 84%), and the 1.5-mg bedtime-only group (70% and 30%).
If approved, the new formulation will likely have a big impact on EOE patients, according to Dr. Fernandez-Becker. “The treatment that we decide on ultimately is through shared decision-making with the physician and the patient. I have many patients who want to go with diet, but it’s very difficult and it takes a long time to tailor the therapy, and many patients are not interested in proton pump inhibitors. So topical steroids are something that I prescribe a lot for patients,” she said.
The fact that the formulation is based on a drug with a known safety record is encouraging, but more research needs to be done. “I don’t expect that this would be any different, but that’s something that’s going to be studied,” said Dr. Fernandez-Becker.
The study was funded by Ellodi Pharmaceuticals. Dr. Clarke has no relevant financial disclosures. Dr. Fernandez-Becker has no relevant financial disclosures but was a participant in the study.