Relamorelin Improves Symptoms, Gastric Emptying in Diabetic Gastroparesis

By Will Boggs MD

NEW YORK (Reuters Health) - Relamorelin (RM-131) relieves symptoms and improves gastric emptying in patients with diabetes-related gastroparesis, according to results from a randomized, controlled trial.

“There is hope for patients with gastroparesis, a condition for which there is still considerable unmet need, with only one approved drug (metoclopramide, which carries an FDA warning) and essentially experimental treatments that have not been proven to be beneficial in rigorous randomized controlled trials (e.g., pyloric injection of botulinum toxin, gastric peroral endoscopic myotomy (G-POEM), or gastric electrical stimulation),” Dr. Michael Camilleri from Mayo Clinic, Rochester, Minnesota told Reuters Health by email.

Relamorelin is a pentapeptide ghrelin receptor agonist that was shown to accelerate gastric emptying and reduce vomiting in a phase 2A study of patients with diabetic gastroparesis.

Dr. Camilleri and colleagues evaluated the safety and efficacy of twice-daily subcutaneous relamorelin in their 12-week, placebo-controlled trial of 393 patients with diabetic gastroparesis.

The primary endpoint, change in weekly vomiting episodes, did not differ between the relamorelin and placebo groups, but placebo recipients experienced a remarkable 70% improvement (vs. approximately 75% with relamorelin).

“The reason for this high placebo response rate is unclear,” the researchers note, “though it questions the use of number of vomiting episodes as a primary endpoint in studies of diabetic gastroparesis.”

Relamorelin treatment was associated with significant improvements, relative to placebo, in the composite endpoint of nausea, postprandial fullness, abdominal pain, and bloating, as well as in the individual components, according to the July 28 Gastroenterology online report.

Gastric emptying time accelerated by about 10% (half-life decrease, 12-13 minutes, depending on dose) with relamorelin, compared with a <1% change with placebo.

Relamorelin was well tolerated, although there were significantly more hyperglycemia events with relamorelin than with placebo.

“Most interesting is the observation that relamorelin significantly improved the composite as well as individual symptom scores for the predominant chronic symptoms of gastroparesis: nausea, fullness, bloating, and pain,” Dr. Camilleri said. “This effect is not solely attributable to prokinetic action of ghrelin agonist, but it is consistent with the evidence from basic science studies that there are ghrelin receptors on vagal afferents which are inhibited by ghrelin (and presumably the pentapeptide ghrelin agonist, relamorelin).”

He said that relamorelin is entering multicenter phase 3 clinical trials and that “after approval, I would expect relamorelin to become the standard of care.”

“Physicians should first exclude drug-induced gastroparesis induced by opiates, tricyclics, or GLP-1 agonists in diabetic patients and should obtain a valid gastric emptying scintigraphic 4-hour test to diagnose true gastroparesis (idiopathic, diabetic),” Dr. Camilleri added.

Dr. Janaka Karalliedde from Guy’s and St. Thomas’ Hospital, London, UK, who recently described the use of a neurokinin-receptor antagonist to treat refractory diabetic gastroparesis, told Reuters Health by email, “These results are promising; however, further larger and longer-term studies are needed before relamorelin is standard care for diabetic gastroparesis.”

“There is an unmet need for new treatments for diabetic gastroparesis, a complication of diabetes that is often very challenging to manage,” he added. “Physicians need to be aware of the significant burden gastroparesis has on the lives of people with diabetes.”

Motus, maker of relamorelin, supported the study and employed 3 of the 6 authors.

SOURCE: https://bit.ly/2uGneiX

Gastroenterology 2017.

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