The eosinophilic esophagitis (EoE) treatment landscape is poised for significant transformation as several breakthrough therapies advance through late-stage clinical development, offering new hope for the approximately 800,000 patients diagnosed with this chronic inflammatory condition across major markets.
EoE, characterized by eosinophil-dominated inflammation of the esophageal lining, presents with diverse clinical features including varying age of onset, symptoms, disease progression, and treatment responses. The condition is primarily driven by a CD4+ T helper type 2 (Th2) allergic inflammatory reaction to food allergens, according to consistent findings from both clinical and experimental studies.
Current Treatment Landscape
Current treatment approaches for EoE include dietary modifications, medications, and endoscopic procedures. The pharmacological options remain limited, with proton pump inhibitors (PPIs) and corticosteroids commonly prescribed despite their association with high relapse rates.
Only two medications have received regulatory approval specifically for EoE:
DUPIXENT (dupilumab), developed by Regeneron and Sanofi, is a human IgG4 monoclonal antibody that blocks IL-4 and IL-13 signaling by targeting the IL-4Rα subunit. The U.S. FDA initially approved DUPIXENT for EoE in May 2022 for adults and adolescents aged 12 and older weighing at least 40 kilograms. In January 2024, this indication was expanded to include children as young as 1 year old with EoE.
JORVEZA (budesonide), developed by Dr. Falk Pharma GmbH, is a non-halogenated glucocorticoid that received marketing authorization for treating EoE in adults over 18 years old in January 2018. The recommended dosage for acute treatment is two 1 mg tablets twice daily.
Despite these approvals, gastroenterologists often hesitate to incorporate these medications into routine clinical practice due to concerns about safety and efficacy profiles, as well as the lack of standardized dosing guidelines.
Emerging Therapies Showing Promise
Three investigational therapies are generating significant interest for their potential to address the limitations of current treatments:
APT-1011 (Ellodi Pharmaceuticals)
APT-1011 represents an innovative approach to EoE treatment as an oral formulation of fluticasone utilizing Adare's proprietary AdvaTab technology. This formulation enables targeted topical delivery to the esophagus, potentially improving efficacy while minimizing systemic exposure.
The therapy has received both Orphan Drug Designation from the FDA and EMA, along with Fast Track Designation from the FDA. These designations were supported by clinical data demonstrating histological remission and symptom improvement following a 12-week induction phase, with sustained maintenance of these benefits.
Following successful completion of the FLUTE 1 (Phase IIb) and FLUTE 2 (Phase III) studies, Ellodi Pharmaceuticals has initiated FLUTE 3, a second Phase III trial that is currently ongoing.
Dr. Evan Dellon, Professor of Medicine and Epidemiology at the University of North Carolina School of Medicine, noted in a recent presentation, "The targeted delivery mechanism of APT-1011 represents a significant advancement in how we approach topical steroid therapy for EoE, potentially improving patient outcomes while minimizing systemic exposure."
TEZSPIRE (tezepelumab) - AstraZeneca
TEZSPIRE is a potentially first-in-class human monoclonal antibody that targets thymic stromal lymphopoietin (TSLP), a key cytokine that initiates multiple inflammatory pathways implicated in EoE pathogenesis.
The drug has received Orphan Drug Designation from the FDA for EoE treatment and is currently being evaluated in the Phase III CROSSING clinical trial to assess its efficacy and safety in EoE patients.
"By targeting TSLP, tezepelumab addresses inflammation at an earlier point in the inflammatory cascade than existing biologics, potentially offering a more comprehensive approach to controlling the underlying disease process," explained Dr. Marc Rothenberg, Director of the Cincinnati Center for Eosinophilic Disorders.
ESO-101 (EsoCap)
ESO-101 represents another novel approach as an esophagus-targeted formulation of mometasone furoate. The drug is designed to enhance mucosal contact and maximize drug deposition in the esophagus, potentially delivering more effective treatment directly to the site of inflammation.
ESO-101 has received Orphan Drug Designation from the FDA and has successfully completed a Phase II trial in EoE, with promising results already published in peer-reviewed literature.
Market Growth Projections
According to a recent market analysis by DelveInsight, the EoE market across the seven major markets (United States, EU5, and Japan) is expected to grow substantially from USD 1.8 billion in 2023 through 2034. This growth is attributed to rising disease awareness, increased diagnosis rates, and incremental healthcare spending worldwide.
The anticipated launch of these emerging therapies is expected to reshape the EoE treatment landscape, offering new standards of care and creating opportunities for medical innovation and economic growth in this therapeutic area.
Unmet Needs and Future Directions
Despite these promising developments, significant unmet needs remain in the EoE treatment landscape. Current diagnostic approaches require invasive endoscopic procedures, and there is a lack of validated biomarkers for monitoring disease activity and treatment response.
Additionally, the heterogeneous nature of EoE suggests that personalized treatment approaches may be necessary to optimize outcomes for individual patients. Research into predictive biomarkers that could guide treatment selection is ongoing but remains in early stages.
"The future of EoE management will likely involve combination approaches tailored to individual patient characteristics," said Dr. Ikuo Hirano, Professor of Medicine at Northwestern University Feinberg School of Medicine. "As we gain a deeper understanding of disease endotypes and treatment response predictors, we'll be better positioned to implement precision medicine approaches for this complex condition."
As these emerging therapies progress through clinical development and potentially reach the market, they promise to expand treatment options for EoE patients and address some of the limitations of current approaches. However, continued research into disease mechanisms, biomarkers, and novel therapeutic targets will be essential to fully address the complex needs of this patient population.
