Rhythm, a biopharmaceutical company, and Actavis plc, a leading global pharmaceutical company, announced the initiation of a phase 2b clinical trial assessing the efficacy and safety of relamorelin (RM-131), Rhythm's ghrelin agonist, for the treatment of gastroparesis in patients with type 1 and type 2 diabetes. Ghrelin is a peptide hormone produced in the stomach that stimulates gastrointestinal (GI) motility. Actavis has an exclusive option to acquire Rhythm's wholly owned subsidiary, Rhythm Pharmaceuticals, Inc., upon the completion of the phase 2b study.

"This is the second of two studies assessing the efficacy and safety of relamorelin for the treatment of diabetic gastroparesis," said Fred Fiedorek, MD, chief medical officer of Rhythm. "This phase 2b study is designed to expand our understanding of RM-131's profile for treating diabetic patients with both moderate and severe gastroparesis, prior to the initiation of phase 3 registration studies."

The phase 2b trial is designed to evaluate the effect of relamorelin on signs and symptoms of gastroparesis, GI motility, and safety in patients with diabetic gastroparesis. The randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of dosing regimens ranging from 10 to 100 mcg administered twice daily over three months. The trial is expected to enroll approximately 400 patients with diabetic gastroparesis at clinical sites in the US and Europe.

Rhythm previously completed two successful phase 2 clinical trials with relamorelin: In a phase 2 trial for diabetic gastroparesis, patients treated with relamorelin 10 mcg twice daily demonstrated statistically significant improvements in gastric emptying and vomiting symptoms, and in a pre-specified subgroup also showed statistically significant improvements in the other symptoms of gastroparesis;  In a separate phase 2a study for chronic constipation, patients treated with relamorelin 100 mcg once daily for two weeks demonstrated statistically significant improvements in spontaneous bowel movements and in lower GI transit. Relamorelin demonstrated a potent prokinetic effect on GI transit in both studies, as well as in phase 1 studies, and was generally well tolerated.

"The need for better treatments for diabetic gastroparesis is pressing," said Keith Gottesdiener, MD, CEO of Rhythm. "This is a debilitating condition that affects several million people in the US, with only one drug approved by the FDA in the past 30 years. Thus far, relamorelin has been shown to directly improve impaired gastric function in our clinical trials, and we are excited about its potential to significantly improve the health of people suffering from this disorder."

"The clinical results with relamorelin in the initial Phase 2 trial in diabetic gastroparesis were precedent-setting," said David Nicholson, executive vice president of global brands research and development for Actavis. "Both Rhythm and Actavis are looking forward to the results from this important trial, and to the positive impact this drug may have on the lives of people with GI functional disorders."

Relamorelin is a phase 2 ghrelin agonist in development for the treatment of diabetic gastroparesis and GI functional disorders. Derived from the natural ghrelin sequence, relamorelin has been optimized to stimulate gastrointestinal (GI) motility, with greater potency and enhanced stability and pharmacokinetics. Relamorelin has completed a phase 2 trial in diabetic gastroparesis and a phase 2a study in chronic constipation, and additional Phase 2 trials are under way in lower GI functional disorders and diabetic gastroparesis. The US Food and Drug Administration (FDA) has granted Fast Track review status to relamorelin for the treatment of diabetic gastroparesis.

Diabetic gastroparesis is a disorder in which there is a substantial delay in stomach emptying with characteristic symptoms of vomiting, nausea, abdominal pain, early satiety, and bloating. Moderate to severe diabetic gastroparesis results in significant debility and hospitalizations and can interfere with nutrition and the absorption of medications. Gastroparesis affects a significant number of the 24 million diabetics in the US; an estimated 2.3 million type 1 and type 2 diabetic patients with moderate or severe gastroparesis symptoms are seeking treatment. Available therapies to treat this disorder are limited and exhibit significant side effects. No new therapies have been approved in the U.S. for the treatment of gastroparesis in more than 30 years.

Rhythm is a biopharmaceutical company developing peptide therapeutics that address unmet needs in gastrointestinal diseases and obesity caused by genetic deficiencies in the MC4 pathway.