Rhythm Presents Positive Phase 2 Study Results for Relamorelin for Chronic Constipation

BOSTON, Oct. 24, 2014 /PRNewswire/ -- Rhythm announced today the presentation of results from a Phase 2a clinical trial assessing the safety and efficacy of relamorelin (RM-131) in 48 patients with chronic constipation. Analysis of the data indicates that relamorelin administered once daily for two weeks in patients with chronic constipation significantly improves constipation symptoms, along with accelerating colonic transit. The study results were presented in a late-breaker session at the American College of Gastroenterology 2014 Annual Scientific Meeting (ACG 2014) in Philadelphia on October 21, 2014.

"The results of this study demonstrate that relamorelin is effective in significantly improving constipation symptoms and accelerating gastric and colonic transit in patients with chronic constipation," said Michael Camilleri, M.D., a gastroenterologist at Mayo Clinic and the senior investigator for the study.*

Rhythm is also conducting a Phase 2a clinical trial for chronic refractory constipation in Parkinson's disease patients. In addition, the company has completed a successful Phase 2 trial of relamorelin for the treatment of diabetic gastroparesis, and expects to initiate a Phase 2b clinical trial for the treatment of diabetic gastroparesis by early 2015.

Study Results
The Phase 2 clinical trial was designed to evaluate efficacy, safety, and pharmacodynamics (upper and lower GI transit) of relamorelin in 48 patients with chronic constipation. The randomized, double-blind, placebo-controlled, parallel-group study assessed relamorelin 100 mcg and placebo administered once daily to patients with chronic constipation over a period of 14 days. The study's primary clinical endpoint was stool consistency based on the Bristol Stool Scale; the study's primary pharmacodynamic endpoint was colonic transit. Other key secondary endpoints included the number of spontaneous bowel movements (SBMs) per week, the number of complete SBMs (SBMs with complete evacuation), ease of passage (straining), and time for first bowel movement (BM) after initiating treatment.

In the oral presentation, "A Phase II, Placebo-Controlled Trial of Efficacy, Safety, and Pharmacodynamics of Relamorelin in Chronic Constipation," Andres Acosta, MD, PhD, Postdoctoral Research Fellow at Mayo Clinic and the lead author on the study, presented the following clinical data:

• Relamorelin increased number of SBMs per week (p=0.002) and complete SBMs per week (p=0.049).
• Relamorelin accelerated the time to first BM after first dosing (p=0.004), improved ease of stool passage (p=0.042), but not stool consistency (p=0.184).
• Relamorelin accelerated gastric emptying (T½ p=0.027), small bowel transit (p=0.051), and colonic transit at 32 hours (p=0.040) and 48 hours (p=0.017).
• Overall, relamorelin was well tolerated, with little evidence of any safety concerns.

"We are excited about these study results because there is a need for new drugs to treat lower GI motility disorders, particularly refractory constipation," said Keith Gottesdiener, MD, CEO of Rhythm. "Relamorelin's prokinetic mechanism of action and good safety profile makes it a compelling clinical candidate for refractory constipation, and also for patients with concurrent upper and lower GI motility dysfunction, both of which are prevalent in patients with Parkinson's disease."

Study Design
This study was a randomized, double-blind, placebo-controlled, parallel-group study, where all patients received single-blinded placebo during a 14-day baseline phase, and those with an average of less than four bowel movements per week during baseline were randomized (1:1) to placebo or relamorelin 100 mcg for the next 14 days. Scintigraphic CT was measured at baseline; the first 24 patients with geometric center (GC) less than 2.4 at 24 hours participated in a pharmacodynamics substudy as well as the clinical trial. From the daily bowel dairy (days 1-28), endpoints were: Time to first bowel movement (BM), number of spontaneous BMs (SBM)/week, BM form (by 1-7 Bristol scale), and ease of BM passage (scale 1-7, with 4 being normal). Gastric emptying (GE), small bowel transit (SBT), and colonic transit (CT) were repeated in the last 2 days of treatment. Statistical analysis used analysis of covariance. As a result, 68 patients entered the baseline period, and 48 (all females) were randomized: Mean age (+/-SEM) 40.6+/-1.5y; and BMI 25.7+/-0.6 kg/m2.

About Relamorelin (RM-131)
Relamorelin is a potent, best-in-class, 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 an additional Phase 2 trial is under way in lower GI functional disorders. The U.S. Food and Drug Administration (FDA) has granted Fast Track review status to relamorelin for the treatment of diabetic gastroparesis.

About Lower GI functional Disorders
Up to 19% of the U.S. population seeks medical care annually for chronic constipation and IBS, and approximately 38% of this group is dissatisfied with traditional treatment options due to lack of efficacy. These conditions are two of the most common GI functional disorders, with significant health consequences and symptoms including constipation, abdominal pain, nausea, bloating, and decreased appetite. Ongoing relamorelin lower GI clinical trials focus on refractory constipation, including refractory constipation in patients with Parkinson's disease. Approximately one million people in the United States are living with Parkinson's disease. Constipation is common among patients with Parkinson's disease, with studies reporting that more than 50% of patients suffer from moderate to severe constipation, many of whom are refractory to existing therapies. In addition, GI functional disorders in Parkinson's disease patients can affect the upper GI tract, resulting in gastroparesis symptoms. GI functional disorders in Parkinson's disease patients also may undermine the GI absorption of L-DOPA, interfering with this drug's efficacy in managing the symptoms of Parkinson's disease.

About Rhythm (www.rhythmtx.com)
Rhythm is a biopharmaceutical company developing peptide therapeutics that address unmet needs in gastrointestinal diseases and obesity, including obesity caused by genetic deficiencies in the MC4 pathway. Rhythm is developing the ghrelin peptide agonist, relamorelin (RM-131), for the treatment of diabetic gastroparesis and other gastrointestinal functional disorders; and the MC4R peptide agonist, RM-493, for obesity, including obesity caused by genetic deficiencies in the MC4 pathway. Rhythm investors include MPM Capital, New Enterprise Associates, Third Rock Ventures, Ipsen, and Pfizer Ventures. The company is based in Boston, Massachusetts.

* Dr. Camilleri has research funded by Rhythm to study relamorelin. He also serves on the company's Scientific Advisory Board. He receives no personal financial compensation from Rhythm.

Contact:
Bart Henderson
President
(857) 264-4281
[email protected]

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