Gastroparesis future or investigational therapies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

• In patients with diabetic gastroparesis, ghrelin and motilin receptors, are the two key pharmacological targets, that have emerged for novel therapeutic options.
• The intravenously administered cyclic ghrelin analog, TZP-101, was demonstrated to accelerate gastric emptying and improve symptom severity when compared with placebo.
• When studied in a phase IIa clinical trial, the oral counterpart, TZP-102, showed promise in that significant improvement in symptoms were seen (although there was no change in gastric emptying) after 4 weeks of treatment
• The follow-up 12-week phase IIb trial 76 failed to demonstrate a benefit; however, and it seems further investigation of this agent is not being pursued.
• Relamorelin (RM-131) is a synthetic small molecule ghrelin agonist which, when administered as a one-time subcutaneous injection, has been demonstrated to accelerate gastric emptying in patients with diabetic GP.
• In a 4-week, phase II clinical trial, twice daily relamorelin improved gastric emptying as measured by breath testing and improved subjective vomiting severity as compared with placebo.
• Other GP symptom measurements were not significantly improved, however, Camicinal (GSK962040) is a small molecule selective motilin receptor agonist that was developed based on the mechanism and molecular structure of macrolide antibiotics.
• Camicinal improves gastric empting in diabetic GP as demonstrated in several phase I clinical trials 80 and preliminary results of a phase II clinical trial demonstrates significant symptom improvement above placebo.

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