Relamorelin for the treatment of gastrointestinal motility disorders

ABSTRACT

Introduction: Current treatments for gastroparesis are limited. Chronic idiopathic constipation (CIC) has more treatment options, but none are efficacious for severe cases.

Areas covered: Molecular targets to accelerate GI motility are being identified, and relamorelin, a synthetic ghrelin analog, has been promising. In humans, relamorelin increases growth hormone levels and accelerates gastric emptying. Relamorelin was superior to placebo for symptom relief in phase IIA studies for diabetic gastroparesis (DG) and CIC. In phase IIB studies in DG, relamorelin did not significantly reduce vomiting frequency when compared to placebo, but it reduced four symptoms of DG (nausea, fullness, bloating and abdominal pain) and accelerated gastric emptying. To date, relamorelin has been well tolerated and safe in humans without cardiac or neurologic adverse effects. It is still in clinical trial stages and not yet approved by the Food and Drug Administration. Phase III studies are underway.

Expert opinion: Relamorelin shows promise in treating DG, with a reduction in core symptoms. Relative to available treatments, it appears to be efficacious and well tolerated. The absence of neurological or cardiovascular adverse effects places it at an advantage over other available therapies. Once approved, it will likely become the drug of first choice for DG.

KEYWORDS:

• Gastroparesis
• diabetic
• chronic idiopathic constipation
• ghrelin
• growth hormone
• receptor

Article highlights

• Ghrelin receptors are identified throughout the gastrointestinal tract in several species including humans

• Relamorelin is a pentapeptide ghrelin analog with prokinetic properties

• Relamorelin accelerates gastric emptying in patients with type 1 and type 2 diabetes who have upper gastrointestinal symptoms

• Relamorelin relieves pivotal symptoms such as vomiting (phase IIA trial) and individual and composite symptoms scores (nausea, bloating, fullness, pain - phase IIB trial) in patients with diabetic gastroparesis

• Relamorelin accelerates gastric, small bowel and colonic transit, stimulates colonic contractions and relieves constipation in patients with chronic constipation

• Relamorelin appears to be safe, is associated with high patient compliance, and is devoid of neurological or cardiac adverse effects

This box summarizes key points contained in the article.

Declaration of interest

M. Camilleri has received research funding from Rhythm Pharmaceuticals for studies of pharmacodynamics of relamorelin. M. Camilleri has also performed consulting for Rhythm Pharmaceuticals, with the consulting fee going to his employer, Mayo Clinic. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.