The Unmet Need for New Gastroparesis Medications
Gastroparesis is a chronic digestive disorder characterized by delayed stomach emptying, leading to symptoms like nausea, vomiting, bloating, and abdominal pain. Its causes can range from diabetes and surgical complications to unknown origins (idiopathic). For over 40 years, metoclopramide has been the only drug explicitly FDA-approved for this condition in the U.S., but it carries significant side effects, including the risk of tardive dyskinesia with long-term use. This creates a high demand for safer, more effective treatments, driving significant research into new pharmacological options.
The Tradipitant Rejection: A Recent Setback
One of the most anticipated new drug candidates for gastroparesis was tradipitant, developed by Vanda Pharmaceuticals. It is a neurokinin-1 receptor (NK-1R) antagonist, a novel mechanism intended to address symptoms like nausea and vomiting by acting on both the gastrointestinal tract and the brain. In December 2023, the FDA accepted Vanda's New Drug Application (NDA), raising hopes for the first new approval in decades.
However, in September 2024, the FDA issued a Complete Response Letter (CRL), declining to approve the drug and requesting additional efficacy studies. Despite positive Phase 2 results and data from open-label studies suggesting symptom improvement, particularly in nausea, the Phase 3 trial failed to meet statistical significance for its primary endpoint. The company is currently contesting the FDA's decision, highlighting the ongoing challenges in bringing new gastroparesis treatments to market.
Promising Drug Candidates in Development
While the tradipitant setback is disappointing, several other investigational drugs are advancing through the clinical pipeline, offering renewed hope for patients.
Naronapride: A Dual-Action Prokinetic
Naronapride (ATI-7505) is an oral, dual-action prokinetic medication designed to target both the serotonin type 4 (5-HT4) and dopamine-2 (D2) receptors. Its unique approach aims to accelerate gastric emptying with potentially fewer side effects than metoclopramide, which also acts on D2 receptors but can cause neurological issues.
Key facts about naronapride:
- Status: A global Phase 2b trial (MOVE-IT) comparing different doses of naronapride to a placebo was completed in May 2025, evaluating efficacy, safety, and tolerability.
- Mechanism: Acts locally within the gut to stimulate motility while minimizing systemic absorption, which is intended to reduce central nervous system side effects.
- Patient Population: The MOVE-IT study enrolled patients with both idiopathic and diabetic gastroparesis.
Relamorelin: A Ghrelin Receptor Agonist
Relamorelin is a synthetic peptide that mimics the effects of the hormone ghrelin, a molecule involved in stimulating appetite and regulating gastrointestinal motility. As a ghrelin receptor agonist, it is designed to accelerate gastric emptying and address core gastroparesis symptoms.
Key facts about relamorelin:
- Status: It has shown promising results in Phase 2 trials for diabetic gastroparesis, demonstrating significant improvement in symptoms like vomiting and accelerated gastric emptying compared to a placebo.
- Mechanism: Stimulates gastrointestinal motility by activating ghrelin receptors.
- Outlook: Although further trials are required and FDA approval is not yet secured, relamorelin remains a promising candidate, particularly for diabetic gastroparesis.
Comparison of Pharmacological Options for Gastroparesis
| Feature | Metoclopramide | Erythromycin | Tradipitant | Naronapride | Relamorelin |
|---|---|---|---|---|---|
| Mechanism | Dopamine D2 antagonist and 5-HT4 agonist | Motilin receptor agonist | Neurokinin-1 (NK-1) receptor antagonist | 5-HT4 agonist and D2 antagonist | Ghrelin receptor agonist |
| Approval Status (US) | Oral tablets and nasal spray (Gimoti) approved | Used off-label; loses efficacy over time | NDA denied by FDA in 2024; future uncertain | Phase 2b clinical trials completed (2025) | Phase 2 trials showed promise; ongoing research |
| Key Benefits | Only FDA-approved long-term treatment option | Effective prokinetic, but short-term use | Symptom management, especially nausea | Dual-action with potentially lower systemic side effects | Accelerates gastric emptying, reduces vomiting |
| Key Limitations | Black box warning for tardive dyskinesia | Tachyphylaxis (decreasing effect over time) and diarrhea | Failed to show statistical significance in Phase 3 trial | Still in development; efficacy and safety data pending | Still in development; focuses primarily on diabetic gastroparesis |
Beyond Pharmacology: Advanced and Endoscopic Therapies
For patients with severe or refractory gastroparesis, non-pharmacological interventions provide additional avenues for treatment. These procedures, often reserved for those who have not responded to medication, are continually advancing.
Endoscopic Pyloromyotomy (G-POEM)
This minimally invasive endoscopic procedure involves cutting the muscle at the pylorus, the outlet of the stomach, to improve stomach emptying. It has shown promise in clinical studies and offers a potential long-term solution for symptoms.
Gastric Electrical Stimulation (GES)
GES involves surgically implanting a device that delivers mild electrical pulses to the stomach muscles. Approved by the FDA for humanitarian use, it can help manage chronic nausea and vomiting, particularly in diabetic and idiopathic gastroparesis patients. Ongoing studies aim to optimize its effectiveness.
Conclusion: A Difficult but Hopeful Path Forward
The search for what is the new drug for gastroparesis highlights both the significant need and the complex challenges involved in finding effective treatments. The recent rejection of tradipitant by the FDA is a notable disappointment, but it does not signal a halt in progress. The ongoing clinical trials for new pharmacological agents like naronapride and relamorelin, combined with advancements in endoscopic and surgical procedures such as G-POEM and GES, provide cautious optimism for patients. As research continues and our understanding of gastroparesis deepens, the landscape of treatment options will hopefully evolve, bringing much-needed relief to those living with this debilitating condition. For more information and patient resources, the International Foundation for Gastrointestinal Disorders (IFFGD) offers valuable support and advocacy.
The Role of GLP-1 Agonists
In recent years, the widespread use of GLP-1 agonists like semaglutide (Ozempic, Wegovy) for diabetes and weight loss has introduced a new complication for some patients: delayed gastric emptying. While these drugs are not a cause of gastroparesis in all users, they can exacerbate existing conditions or cause gastroparesis-like symptoms. This has spurred further investigation into the interaction between these new classes of drugs and gastric motility disorders.
