Date: 2016-10-27
Type of information: Results
phase: 2b
Announcement: results
Company: Actavis (Ireland) Rhythm, now Motus Therapeutics (USA - IL)
Product: relamorelin (RM-131)
Action
mechanism: peptide/ghrelin agonist. 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 FDA has granted Fast Track review status to relamorelin for the treatment of diabetic gastroparesis.
Disease: gastroparesis in patients with type 1 and type 2 diabetes
Therapeutic area: Gastrointestinal diseases - Metabolic diseases
Country: USA
Trial
details: 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 is evaluating the safety and efficacy of dosing regimens ranging from 10 to 100 mcg administered twice daily over three months. (NCT02357420)
Latest
news: * On October 27, 2016, Allergan and Rhythm Holding Company, which owns Motus Therapeutics, announced the top line results of a Phase 2b clinical trial assessing the efficacy and safety of relamorelin (RM-131) , Motus' ghrelin agonist, for the treatment of gastroparesis in patients with type 1 and type 2 diabetes. * On April 4, 2016, Motus Therapeutics announced the completion of enrollment for a Phase 2b clinical trial assessing the efficacy and safety of relamorelin (RM-131) for the treatment of gastroparesis in patients with type 1 and type 2 diabetes. Allergan has an exclusive option to acquire Motus Therapeutics, Inc. upon the completion of this Phase 2b study. Prior to this study, Motus completed a Phase 2a trial of relamorelin in 204 patients with diabetic gastroparesis that 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. * On April 8, 2015, Rhythm and Actavis 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. 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 U.S. 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.
In the study, relamorelin administered for 12 weeks demonstrated substantial efficacy for the key diabetic gastroparesis symptoms of nausea, post-prandial fullness, abdominal pain and bloating (measured both individually and as a composite endpoint), along with a potent prokinetic effect on gastric motility. Patients receiving relamorelin also experienced an approximately 75 percent reduction in vomiting frequency across all doses compared to baseline (the primary endpoint), similar to the effect seen in the Phase 2a trial. However, an unusually high placebo response for vomiting frequency, extending well beyond that expected from previous studies, limited the ability to demonstrate treatment efficacy on the vomiting frequency endpoint.
The Phase 2b trial was designed to evaluate the effect of relamorelin on the key signs and symptoms of gastroparesis identified in the draft FDA guidance for gastroparesis, as well as gastric emptying and safety in patients with moderate to severe diabetic gastroparesis and with symptoms of vomiting at baseline. The trial enrolled 393 patients with diabetic gastroparesis at clinical sites in the U.S. and Europe .
Overall, relamorelin was safe and well-tolerated in the phase 2b study with high compliance and completion rates over the course of the study. There was some evidence of dose-related adverse events related to worsening of glycemic control in some patients.
Motus Therapeutics previously completed a successful 4-week Phase 2 clinical trial of relamorelin in diabetic gastroparesis, in which patients treated with relamorelin 10 mcg twice daily demonstrated statistically significant improvements in gastric emptying and vomiting frequency and in a pre-specified subgroup also showed statistically significant improvements in the other symptoms of gastroparesis.
Rhythm Holding and Allergan plan to submit the data for presentation at a major gastrointestinal medical conference in 2017. In addition, Allergan has exercised its option to acquire Motus Therapeutics and intends to initiate Phase 3 clinical trials of relamorelin.
