USFDA Guidance: GERD-Related Drug Development: A Comprehensive Update

The U.S. Food and Drug Administration (FDA) released three important draft guidances on September 11, 2025, providing updated recommendations for drug development programs targeting GERD-related conditions and disseminated coccidioidomycosis. These documents outline approaches for clinical trial design, efficacy evaluation, and safety considerations.

The draft guidances are available here:

• Disseminated Coccidioidomycosis: Developing Drugs for Treatment

• Symptomatic Nonerosive GERD: Developing Drugs for Treatment

• Erosive Esophagitis: Developing Drugs for Treatment

Key Highlights from the Draft Guidances

1. Symptomatic Nonerosive GERD (sGERD)

The FDA’s draft guidance addresses treatment for patients with typical GERD symptoms such as heartburn or regurgitation, but without visible esophageal damage.

• Trial Population: Adults with persistent symptoms, normal mucosa on baseline endoscopy, and ≥6 months of heartburn history.

• Efficacy Endpoints:

  • Primary: Proportion of heartburn-free days.

  • Secondary: Regurgitation relief via validated patient-reported outcome measures.

• Trial Design: Randomized, double-blind, placebo-controlled; duration 8–12 weeks.

• Safety Considerations: Long-term acid suppression risks, including fractures, infections, and nutrient malabsorption.

  
  

2. Erosive Esophagitis (EE)

The draft guidance provides a roadmap for developing drugs aimed at both healing and maintaining remission in erosive esophagitis, a severe GERD subtype.

• Trial Population: Patients diagnosed with erosive disease using the Los Angeles (LA) Classification system (Grades A–D).

• Efficacy Endpoints:

  • Healing Phase: Endoscopic confirmation of complete mucosal healing.

  • Maintenance Phase: Sustained healing and symptom relief.

• Trial Design: Randomized, double-blind, active comparator trials preferred; noninferiority or superiority approaches recommended.

• Safety Considerations: At least 8 weeks of healing data and 24 weeks of maintenance data required.

  
  

3. Disseminated Coccidioidomycosis

The FDA’s draft guidance focuses on clinical development of antifungal drugs for systemic fungal infection caused by Coccidioides species.

• Trial Population: Patients with confirmed disseminated disease (excluding isolated pulmonary cases).

• Trial Design: Controlled studies recommended, with endpoints measuring clinical response, fungal clearance, and survival rates.

• Safety Considerations: Long-term antifungal safety, drug–drug interactions, and monitoring for treatment-related toxicities.

  
  

Why These Updates Matter

• Patient-Centered Outcomes: Emphasis on heartburn-free days and patient-reported measures ensures outcomes reflect real patient experience.

• Improved Trial Rigor: Active comparator and noninferiority trial designs in EE programs raise the scientific standard.

• Long-Term Safety Focus: Each draft guidance highlights the need for robust safety databases.

• Targeted Development: Tailored strategies distinguish between nonerosive GERD, erosive GERD, and fungal infections, supporting condition-specific drug pathways.

The September 11, 2025 FDA draft guidances offer much-needed clarity for developers of therapies addressing GERD and disseminated coccidioidomycosis. By focusing on robust trial design, meaningful endpoints, and safety evaluation, the FDA is paving the way for innovative, patient-centered treatments.

Sponsors are encouraged to review the full documents and submit comments within 60 days of Federal Register publication.