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Erosive Esophagitis: Developing Drugs for Treatment: Draft Guidance for Industry

DraftCenter for Drug Evaluation and Research09/17/2025

Description

The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a draft guidance for industry entitled “Erosive Esophagitis: Developing Drugs for Treatment.” The draft guidance details recommendations on clinical trials for drugs being developed for the healing of erosive esophagitis (EE) and maintenance of healed EE in adults, including considerations for eligibility criteria, trial design features, efficacy evaluations, and safety assessments.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

4
Tricyclic antidepressants

Drugs with significant anticholinergic effects

Histamine H2-receptor antagonists

Concomitant acid-reducing medications

Proton pump inhibitors

Concomitant acid-reducing medications

Therapeutic biological products

Licensed under section 351 of the Public Health Service Act.

Stakeholders

2
Sponsors

Assist sponsors in the nonclinical evaluation

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

2
Clinical trial

Administering survey instruments in a clinical trial at screening and/or exit visits; obtaining patient feedback regarding various topics throughout a trial

Clinical development

The process of developing drugs for treatment of EE.

Document Types

1
Patient-reported outcome measure

Instrument used to assess symptoms like heartburn and regurgitation

Attributes

5
Grade D

Mucosal break involving at least 75% of the esophageal circumference.

Grade C

Mucosal break continuous between tops of two or more mucosal folds involving less than 75% circumference.

Grade B

Mucosal break more than 5 mm long not extending between tops of two mucosal folds.

Grade A

Mucosal break no longer than 5 mm not extending between tops of two mucosal folds.

Type I error rate

Statistical parameter requiring strong control when testing multiple endpoints

Technical Details

Substances

2
Helicobacter pylori

Subjects testing positive for this during screening should be excluded

Investigational product

The drug being tested in clinical trials.

Testing Methods

3
Endoscopic Assessment

The procedure used to apply the Los Angeles Classification criteria.

Endoscopy

Method used to document healed EE and assess primary endpoints

Endoscopic evaluation

Used to define EE by the presence of superficial esophageal erosions.

Clinical Concepts

10
Esophageal circumference

Anatomical reference used to distinguish between Grade C and Grade D esophagitis.

Mucosal break

The primary clinical observation used to define grades A through D in the LA Classification.

Osteoporosis-related bone fractures

Potential risk identified with long-term acid suppression

Clostridioides difficile enteric infections

Potential risk identified with long-term acid suppression

Eosinophilic esophagitis

Coexisting disease affecting the esophagus

Gastric ulcers

Exclusion criterion for the trial

Barrett's esophagus

Potential progression from untreated erosive esophagitis.; Exclusion criterion for the trial

Esophageal strictures

Complication of untreated erosive esophagitis.

Gastroesophageal reflux disease

Spectrum of acid-related disorders including EE.

Erosive Esophagitis

The primary disease state addressed by the guidance.; Primary disease state being treated in the clinical trials; The clinical condition being assessed via endoscopic grading.

Standards & References

External Standards

2
Los Angeles Classification of Esophagitis

A system used for the endoscopic assessment and grading of erosive esophagitis.

Los Angeles classification system

System used to define and grade EE severity at baseline endoscopy.

Specifications

2
LA Grade

Los Angeles classification used to assess disease severity

LA Grade A-D

Spectrum of disease severity for enrollment criteria.

ICH References (1)

ICH E9(R1)

Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Erosive Esophagitis: Developing Drugs for Treatment: Draft Guidance for Industry | Guideline Explorer | BioRegHub