relamorelin (RM-131) / AbbVie - LARVOL DELTA

Peptide Drug Design Using Alchemical Free Energy Calculation: An Application and Validation on Agonists of Ghrelin Receptor. (PubMed, J Chem Inf Model) - "Along with the calculation, the synthesis and in vitro EC50 activity of relamorelin and 17 new peptide derivatives were also reported...The average of three TI repeats yielded a mean absolute error of 0.98 kcal/mol and Pearson's correlation coefficient (R) of 0.77 against the experimental free energy derived from the in vitro EC50 activity, showing good repeatability of the proposed method and a slightly better agreement than the results obtained from the arbitrary time frames up to 20 ns. Although it is limited by having one target and a deduced binding pose, we hope that this study can add some insights into alchemical free energy calculation of protein-peptide systems, providing theoretical assistance to the development of peptide drugs."

Journal

Relamorelin in Gastroparesis and Diabetic Gastroparesis: A Meta-Analysis on Its Efficacy and Safety. (PubMed, Cureus) - "Despite these adverse effects, the study concludes that relamorelin offers a promising avenue for gastroparesis treatment, especially given the limited existing therapeutic options. This comprehensive meta-analysis synthesizes existing evidence to inform clinical practice and guides future research in this domain."

Journal • Retrospective data • Review • Gastrointestinal Disorder • Pain

Diabetic Gastroparesis and its Emerging Therapeutic Options: A Narrative Review of the Literature. (PubMed, Cureus) - "Tradipitant and relamorelin are two such treatment options that are gaining noteworthy recognition and are discussed in detail in this review article. This leads to an improvement in the quality of life, making it a reliable treatment option for this disease. But while pharmacological intervention is vital, psychological support and lifestyle changes are equally important and are the reason why a multidisciplinary approach is required for the treatment of DG."

Journal • Review • Diabetes • Gastrointestinal Disorder • Metabolic Disorders • Pain

Pharmacotherapeutic advances for chronic idiopathic constipation in adults. (PubMed, Expert Opin Pharmacother) - "Among emerging agents, elobixibat, a drug blocking the reabsorption of bile acids, is a promising one, especially in slow transit constipation. Linaclotide, lubiprostone and plecanatide, by a secretacogue action, improve stool consistency and increase colonic transit. Apart from prucalopride, approved in Europe for refractory chronic idiopathic constipation patients, the selective 5-HT4 agonists velusetrag and naronapride are in advanced development. In addition, relamorelin, a ghrelin agonist, seems promising for accelerating colonic transit...On the other hand, the experience with these new agents is still limited, especially for long-term treatment. Another important point is that these new treatments for chronic idiopathic constipation are not available worldwide and their use could be somewhat limited by their still relatively high cost."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Current Treatment Options and Therapeutic Insights for Gastrointestinal Dysmotility and Functional Gastrointestinal Disorders. (PubMed, Front Pharmacol) - "More comprehensive, large-scale, and longitudinal studies utilizing multi-omics data are needed to dissect the exact contribution of gut microbial alterations in disease pathogenesis. Accordingly, we review the current treatment options, clinical insight on pathophysiology, therapeutic modalities, current challenges, and therapeutic clues for the clinical care and management of functional dyspepsia, gastroparesis, irritable bowel syndrome, functional constipation, and functional diarrhea."

Journal • Review • CNS Disorders • Constipation • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Immunology • Transplantation

New Developments in Prokinetic Therapy for Gastric Motility Disorders. (PubMed, Front Pharmacol) - "The recommended use of metoclopramide, the only currently approved medication for gastroparesis in the United States, is for a duration of less than 3 months, due to the risk of reversible or irreversible extrapyramidal tremors. Domperidone, a dopamine D2 receptor antagonist, is available for prescription through the FDA's program for Expanded Access to Investigational Drugs...Novel targets with potential to improve gastric motor functions include the pylorus, macrophage/inflammatory function, oxidative stress, and neurogenesis. In the current review, we discuss the use of pharmacological approaches with potential to enhance motor functions in the management of gastroparesis."

Journal • Review • Dyspepsia • Gastrointestinal Disorder • Movement Disorders • DRD2

Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data. (PubMed, Aliment Pharmacol Ther) - P2, P2b | "Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin-treated patients."

Clinical • Journal • P2a data • Diabetes • Gastrointestinal Disorder • Metabolic Disorders • Type 2 Diabetes Mellitus

A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis Study 03 (clinicaltrials.gov) - P3; N=467; Terminated; Sponsor: Allergan; N=960 ➔ 467; Trial completion date: Aug 2022 ➔ Oct 2020; Enrolling by invitation ➔ Terminated; Trial primary completion date: Aug 2022 ➔ Oct 2020; The Relamorelin program is being terminated solely based on a business decision.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Gastrointestinal Disorder • Metabolic Disorders

A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis Study 04 (clinicaltrials.gov) - P3; N=451; Terminated; Sponsor: Allergan; Trial completion date: Jul 2021 ➔ Oct 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Jul 2021 ➔ Oct 2020; The Relamorelin program is being terminated solely based on a business decision.

Clinical • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Gastrointestinal Disorder • Metabolic Disorders

Diabetic Gastroparesis Study 05 (clinicaltrials.gov) - P3; N=202; Terminated; Sponsor: Allergan; N=1000 ➔ 202; Trial completion date: Sep 2024 ➔ Oct 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Sep 2024 ➔ Oct 2020; The Relamorelin program is being terminated solely based on a business decision.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Disorder

Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis Study 02 (clinicaltrials.gov) - P3; N=311; Terminated; Sponsor: Allergan; N=600 ➔ 311; Trial completion date: Sep 2021 ➔ Sep 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Sep 2021 ➔ Sep 2020; The Relamorelin program is being terminated solely based on a business decision

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Gastrointestinal Disorder • Metabolic Disorders

A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis 01 (clinicaltrials.gov) - P3; N=336; Terminated; Sponsor: Allergan; N=600 ➔ 336; Trial completion date: Sep 2021 ➔ Sep 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Sep 2021 ➔ Sep 2020; The Relamorelin program is being terminated solely based on a business decision.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Gastrointestinal Disorder • Metabolic Disorders

Diabetic gastroparesis: An overview of pathogenesis, clinical presentation and novel therapies, with a focus on ghrelin receptor agonists. (PubMed, J Diabetes Complications) - "Metoclopramide improves symptoms of gastroparesis although extended treatment presents challenges such as decreased efficacy over time and increased risks for adverse events. We summarize the current knowledge of the pathophysiology of diabetic gastroparesis and review current and investigational treatments for diabetes gastroparesis."

Clinical • Journal • Review • Diabetes • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Metabolic Disorders

Pharmacological Approaches to Diabetic Gastroparesis: A systematic review of randomised clinical trials. (PubMed, Sultan Qaboos Univ Med J) - "Their results revealed that metoclopramide was the only approved drug for accelerating gastric emptying and improving disease symptoms. Preliminary data indicated that relamorelin and prucalopride are novel candidates that have proven to be effective and safe. Future RCTs should be conducted based on unified guidelines using universal diagnostic modalities to reveal reliable and comprehensive outcomes."

Clinical • Journal • Review • Cardiovascular • Diabetes • Metabolic Disorders

Phase 2 Study to Evaluate Safety and Efficacy of RM-131 Administered to Patients With Chronic Constipation - P2; N=48; Completed; Sponsor: Rhythm Pharmaceuticals, Inc.; Active, not recruiting -> Completed

Relamorelin to Treat Constipation: "Pusher" or Pushover? (PubMed) - No abstract available.

Journal • Biosimilar

A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis Study 04 (clinicaltrials.gov) - P3; N=600; Active, not recruiting; Sponsor: Allergan; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Diabetes • Metabolic Disorders

Diabetic Gastroparesis Study 05 (clinicaltrials.gov) - P3; N=1000; Active, not recruiting; Sponsor: Allergan; Enrolling by invitation ➔ Active, not recruiting

Clinical • Enrollment closed • Diabetes

A randomized trial of relamorelin for constipation in Parkinson's disease (MOVE-PD): Trial results and lessons learned. (PubMed) - Parkinsonism Relat Disord - "Although recruitment goals were not met, which precluded demonstration of any potential beneficial effect of relamorelin, unique and important insights with regard to the nature of constipation in PD were recognized, which hopefully will lead to more effective clinical trials in the future. It is clear that what PD patients understand as constipation may be more complex than previously realized and does not appear to be characterized by decreased stool frequency alone."

Journal • Biosimilar • Gene Therapies • Parkinson's Disease

A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis 01 (clinicaltrials.gov) - P3; N=600; Active, not recruiting; Sponsor: Allergan; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Diabetes • Metabolic Disorders

Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis Study 02 (clinicaltrials.gov) - P3; N=600; Active, not recruiting; Sponsor: Allergan; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Diabetes • Metabolic Disorders

CANADIAN INVOLVEMENT IN THE EVALUATION OF NOVEL THERAPY FOR DIABETIC GASTROPARESIS: OVERVIEW OF PLEDGE TRIALS (CDDW 2020) - P3; "Conclusions Canadian centers are actively involved in the PLEDGE trials to help determine the efficacy and safety of RLM, a potential new treatment for DG. This publication increases awareness of the Canadian gastroenterology community, providing an option to refer interested patients to PLEDGE study centers.PLEDGE Studies (NCT03285308, NCT03426345, NCT03420781, NCT03383146, NCT03786380): Placebo-controlled, randomized RLM-MD-01/02/03/04 and open-label study 3071-305-020 to study the safety and efficacy of relamorelin for the treatment of diabetic gastroparesis Funding Agencies None"

A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis Study 03 (clinicaltrials.gov) - P3; N=960; Enrolling by invitation; Sponsor: Allergan; Trial completion date: Dec 2020 ➔ Aug 2022; Trial primary completion date: Dec 2020 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date

Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis Study 02 (clinicaltrials.gov) - P3; N=600; Recruiting; Sponsor: Allergan; Trial completion date: Jan 2020 ➔ Sep 2021; Trial primary completion date: Jan 2020 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date

A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis 01 (clinicaltrials.gov) - P3; N=600; Recruiting; Sponsor: Allergan; Trial completion date: Nov 2019 ➔ Sep 2021; Trial primary completion date: Nov 2019 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date