Why Rebamipide Is Not Approved by the FDA
Rebamipide has not been approved by the FDA primarily because it lacks sufficient high-quality clinical trial data demonstrating its safety and efficacy according to FDA standards, despite being approved and used in several Asian countries for gastrointestinal conditions.
Background on Rebamipide
Rebamipide is a gastroprotective drug that was developed in Japan and has been used in several Asian countries for the treatment of:
- Gastric ulcers
- Chronic gastritis
- Erosive gastritis
- Prevention of NSAID-induced gastrointestinal injuries
- Adjunctive therapy for H. pylori eradication 1
Reasons for Lack of FDA Approval
1. Insufficient Clinical Trial Data for US Standards
- Unlike FDA-approved medications that undergo extensive clinical trials specifically designed to meet FDA requirements, rebamipide's clinical data comes primarily from studies conducted in Asian populations
- The FDA typically requires multiple large-scale, well-controlled clinical trials conducted in diverse populations that demonstrate both efficacy and safety
2. Regional Regulatory Differences
- Regulatory standards and approval processes differ between countries
- Similar to baricitinib, which is approved in some countries but not by the FDA for certain indications like atopic dermatitis 2, rebamipide has not met the specific regulatory requirements for the US market
3. Pharmacokinetic Considerations
- While rebamipide has demonstrated bioequivalence between its different formulations (tablets and granules) 3, the overall pharmacokinetic and pharmacodynamic data may not be robust enough by FDA standards
4. Market Factors
- Pharmaceutical companies must weigh the significant investment required for FDA approval against potential market returns
- With multiple established treatments already available in the US for gastric conditions, the financial incentive to pursue FDA approval may be limited
Mechanism of Action and Potential Benefits
Despite lacking FDA approval, rebamipide has several documented mechanisms of action:
- Stimulates prostaglandin generation in gastric mucosa
- Increases gastric mucus glycoprotein components
- Stimulates migration and proliferation of wounded epithelial cells
- Increases expression of epidermal growth factor and its receptor
- Scavenges active oxygen radicals
- Attenuates neutrophil activity and inflammatory cytokine production 1, 4
Clinical Evidence
Research has shown rebamipide to be effective for:
- Improving ulcer healing, particularly for NSAID-induced ulcers
- Reducing gastric inflammation scores
- Alleviating clinical symptoms of gastritis and ulcers 5
Potential Future Directions
Current research is exploring rebamipide's potential applications in:
- Rheumatoid and gouty arthritis
- Osteoarthritis
- Sjögren's syndrome
- Bronchial asthma
- Vitiligo
- Ophthalmology for corneal epithelium regeneration
- Oncology to reduce inflammatory changes in oral mucosa after chemoradiotherapy 6
Comparison to FDA Approval Process for Similar Drugs
The FDA approval process is rigorous and requires substantial evidence:
- For comparison, medications like upadacitinib and abrocitinib received FDA approval only after demonstrating efficacy and safety in specific patient populations with clear limitations on use 2
- Even established medications like methotrexate remain unapproved by the FDA for certain indications despite widespread off-label use 2
Clinical Implications
For clinicians and patients in the US:
- Alternative FDA-approved medications must be used for conditions where rebamipide might otherwise be considered
- Patients traveling internationally should be aware that medications available in other countries may not be approved or available in the US
- Clinical trials involving rebamipide would be the only legal way to access this medication in the US
Until rebamipide undergoes the necessary clinical trials and regulatory review process specifically designed to meet FDA requirements, it will remain unavailable for prescription use in the United States.