Aemcolo (rifamycin SV MMX) / Cosmo Pharma, RedHill, Dr Falk - LARVOL DELTA

A randomized open label pilot study evaluating the efficacy of two dosing regimens of rifamycin SV MMX in the treatment of small intestinal bacterial overgrowth. (PubMed, BMC Gastroenterol) - "Rifaximin, an antibiotic of the ansamycin class has been shown to be effective in the treatment of SIBO. For clinicians treating SIBO, this study suggests that AEMCOLO is a viable treatment option. A double-blind, placebo-controlled design will probably be necessary to ascertain the true efficacy of different dosing regimens of AEMCOLO in treating SIBO."

Clinical • Journal • Infectious Disease

A Phase II, multicentric, randomized, double-blind, placebo controlled, proof of concept study of efficacy and safety of Rifamycin SV-MMX® 600 mg tablets administered three or two times daily to patients with diarrhea-predominant irritable bowel syndrome (IBS-D). (PubMed, Am J Gastroenterol) - "Rifamycin SV-MMX® 600mg b.i.d. was more effective than placebo and t.i.d. dosing in the first week of treatment. Two months following treatment, Rifamycin SV-MMX® 600mg b.i.d. provided more global symptom relief than placebo."

Clinical • Journal • P2 data • Gastrointestinal Disorder • Pain

Letter to the Editor: Rifamycin SV MMX was superior to placebo, but was the comparison appropriate? (PubMed, Hepatol Commun) - No abstract available

Journal

PHASE II, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, PROOF OF CONCEPT STUDY OF EFFICACY OF RIFAMYCIN SV-MMX® 600 MG ADMINISTERED THREE OR TWO TIMES DAILY TO PATIENTS WITH DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME (IBS-D) (DDW 2024) - "Rifaximin -a non-resorbable antibiotic from the rifamycin group- has been shown to be effective in the treatment of non-constipated IBS patients. In IBS-D, treatment with rifamycin SV-MMX® 600mg b.i.d. was more effective than placebo and t.i.d. dosing in the first week of treatment and provided more adequate relief over the first two months of follow up."

Clinical • P2 data • CNS Disorders • Constipation • Gastrointestinal Disorder • Pain

The RIVET RCT: Rifamycin SV MMX improves muscle mass, physical function, and ammonia in cirrhosis and minimal encephalopathy. (PubMed, Hepatol Commun) - "RiVM is well tolerated in patients with MHE with changes in stool microbial composition and function, ammonia, inflammation, brain oxidative stress, and sarcopenia-related parameters without improvement in cognition. RiVM modulates the gut-brain axis and gut-muscle axis in cirrhosis."

Clinical • Journal • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Inflammation • Sarcopenia • IL1B

RIVET TRIAL: PHASE 2 RCT OF RIFAMYCIN SV MMX, A NOVEL RIFAMPIN ANALOGUE, ON GUT-BRAIN AXIS CHANGES IN CIRRHOSIS AND MINIMAL HEPATIC ENCEPHALOPATHY (AASLD 2023) - "In this phase 2 doubleblind, placebo-controlled RCT of rifamycin SVMMX in patients with cirrhosis and MHE, we found no safety concerns. RiVM Rx resulted in lowered gut microbial α- diversity and cirrhosis dysbiosis ratio. RiVM therapy was associated with reduction in blood ammonia and improved physical function and handgrip."

P2 data • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

Rifamycin in Minimal Hepatic Encephalopathy (clinicaltrials.gov) - P2 | N=32 | Completed | Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center | Recruiting ➔ Completed

Trial completion • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis • IL1B • IL6

Development of a new travellers' diarrhoea clinical severity classification and its utility in confirming Rifamycin-SV efficacy. (PubMed, J Travel Med) - "This newly developed TD clinical severity classification demonstrated strong prognostic value and clinical utility by combining patients' multiple signs and symptoms of enteric infection and number of loose stools to provide a holistic assessment of TD. By expanding on the current classification by incorporating patient reported outcomes in addition to TLUS, a classification like the one developed, may help optimize patient selection for future clinical studies."

Journal • Infectious Disease

Active Clinical Trials in Hepatic Encephalopathy: Something Old, Something New and Something Borrowed. (PubMed, Neurochem Res) - "Among them, there are many old acquaintances in the field, such as lactulose and rifaximin, some new entries such as fecal microbiota transplantation and equine anti-thymocyte globulin, an immunosuppressive agent, but also some therapies borrowed from other conditions, such as rifamycin SV MMX and nitazoxanide, two antimicrobial agents FDA approved for the treatment of some types of diarrheas or VE303 and RBX7455, two microbiome restoration therapies, currently used as treatment of high-risk Clostridioides difficile infections. If working, some of these drugs could soon be used as valid alternatives to current therapies when ineffective or be approved as novel therapeutic approaches to improve the quality of life of HE patients."

Journal • Review • CNS Disorders • Hepatic Encephalopathy • Hepatology • Infectious Disease • Transplantation

Rifamycin in Minimal Hepatic Encephalopathy (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center | Trial completion date: Nov 2022 ➔ Jul 2023 | Trial primary completion date: Sep 2022 ➔ May 2023

Trial completion date • Trial primary completion date • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis • IL1B • IL6

A Randomized Open Label Trial Evaluating the Efficacy of Two Dosing Regimens of Rifamycin SV MMX in the Treatment of Small Intestinal Bacterial Overgrowth (SIBO) (ASTMH 2022) - "Rifaximin, a non-absorbable gut-specific antibiotic with proximal small bowel as site of activity has been used for this purpose with mixed results. A related compound, Rifamycin SV MMX, a member of the ansamycin class of antibiotics, is non absorbable and has activity in the distal small bowel and colon allowing maintenance of the saprophytic bacteria in the proximal small intestine, a microbial milieu which might favor clearance of the overgrowth bacteria...Participants underwent a symptom screening questionnaire and the diagnosis of SIBO was made by a lactulose hydrogen breath test...A positive clinical response was seen in 33% of all participants (17% in arm A and 56% in arm B). Our current findings suggest a higher dosage of rifamycin SV MMX leads to a higher chance of a positive clinical outcome and clearance of SIBO as measured by breath test."

Clinical • Late-breaking abstract • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Pain

Efficacy of AEMCOLO (Rifamycin SV MMX) in the Treatment of Small Intestinal Bacterial Overgrowth (SIBO) (clinicaltrials.gov) - P2 | N=30 | Enrolling by invitation | Sponsor: Bradley Connor | Recruiting ➔ Enrolling by invitation | N=60 ➔ 30 | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Sep 2021 ➔ Dec 2022

Enrollment change • Enrollment status • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Infectious Disease

Evaluate Safety and Efficacy of Rifamycin SV MMX in the Treatment of Traveler's Diarrhea in Children Age 6 to 11 Years (clinicaltrials.gov) - P2 | N=142 | Not yet recruiting | Sponsor: RedHill Biopharma Limited | Trial completion date: Aug 2023 ➔ Dec 2025 | Trial primary completion date: Jun 2023 ➔ Jun 2025

Trial completion date • Trial primary completion date • Gastrointestinal Disorder • Infectious Disease

Study to Evaluate Safety and Efficacy of Rifamycin SV MMX in Treating Traveler's Diarrhea in Children Age 12 to 17 Years (clinicaltrials.gov) - P2 | N=142 | Not yet recruiting | Sponsor: RedHill Biopharma Limited | Trial completion date: Aug 2023 ➔ Dec 2025 | Trial primary completion date: Jun 2023 ➔ Jan 2025

Trial completion date • Trial primary completion date • Gastrointestinal Disorder • Infectious Disease

Rifamycin in Minimal Hepatic Encephalopathy (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center; Trial completion date: Nov 2021 ➔ Nov 2022; Trial primary completion date: Sep 2021 ➔ Sep 2022

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis • IL1B • IL6

[VIRTUAL] RedHill Biopharma (BIO 2021) - "RedHill promotes the gastrointestinal drugs Movantik® (OIC), Talicia® (H. pylori) and Aemcolo® (travelers' diarrhea). RedHill's key clinical late-stage development programs include: (i) RHB-204, with an ongoing Phase 3 study for NTM disease; (ii) opaganib (Yeliva®, ABC294640), a first-in-class SK2 selective inhibitor targeting multiple indications with positive Phase 2 COVID-19 data and an ongoing Phase 2/3 program for COVID-19 and Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing; (iii) RHB-107 (upamostat), a serine protease inhibitor in a U.S. Phase 2/3 study as treatment for symptomatic COVID-19, and targeting multiple other cancer and inflammatory gastrointestinal diseases, as well as additional late-stage asset assets. More information about the Company is available at www.redhillbio.com."

Biliary Cancer • Cholangiocarcinoma • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] DEVELOPMENT OF A NEW TRAVELERS’ DIARRHEA (TD) CLINICAL SEVERITY CLASSIFICATION AND ITS UTILITY IN CONFIRMING RIFAMYCIN SV EFFICACY (DDW 2021) - P3 | "The new TD clinical severity classification provides prognostic information for TD resolution and has potential utility in clinical practice. Rifamycin SV shows efficacy in its moderate/severe categories."

Clinical • Gastrointestinal Disorder • Infectious Disease

Efficacy of AEMCOLO (Rifamycin SV MMX) in the Treatment of Small Intestinal Bacterial Overgrowth (SIBO) (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Bradley Connor; Trial completion date: Mar 2021 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder

Study to Evaluate Safety and Efficacy of Rifamycin SV MMX in Treating Traveler's Diarrhea in Children Age 12 to 17 Years (clinicaltrials.gov) - P2; N=142; Not yet recruiting; Sponsor: RedHill Biopharma Limited; Trial completion date: Jul 2021 ➔ Aug 2023; Trial primary completion date: Jul 2021 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date

Evaluate Safety and Efficacy of Rifamycin SV MMX in the Treatment of Traveler's Diarrhea in Children Age 6 to 11 Years (clinicaltrials.gov) - P2; N=142; Not yet recruiting; Sponsor: RedHill Biopharma Limited; Trial completion date: Jun 2022 ➔ Aug 2023; Trial primary completion date: Jun 2022 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date

Rifamycin in Minimal Hepatic Encephalopathy (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center; Trial completion date: Nov 2020 ➔ Nov 2021; Trial primary completion date: Sep 2020 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis • IL1B • IL6

Rifamycin SV-MMX® 600 mg Tablets Administered Three or Two Times Daily to Patients With IBS-D (clinicaltrials.gov) - P2; N=279; Completed; Sponsor: Cosmo Technologies Ltd; Recruiting ➔ Completed; Trial completion date: Jul 2020 ➔ Dec 2020; Trial primary completion date: May 2020 ➔ Sep 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Disorder • Immunology

Efficacy of AEMCOLO (Rifamycin SV MMX) in the Treatment of Small Intestinal Bacterial Overgrowth (SIBO) (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Bradley A. Connor, M.D.

Clinical • New P2 trial • Gastroenterology • Gastrointestinal Disorder

Rifamycin SV-MMX® 600 mg Tablets Administered Three or Two Times Daily to Patients With IBS-D (clinicaltrials.gov) - P2; N=342; Recruiting; Sponsor: Cosmo Technologies Ltd; Trial completion date: Feb 2020 ➔ Jul 2020; Trial primary completion date: Dec 2019 ➔ May 2020

Clinical • Trial completion date • Trial primary completion date

Rifamycin SV MMX: A Review in the Treatment of Traveller's Diarrhoea. (PubMed, Clin Drug Investig) - "As expected (given its poor systemic absorption), rifamycin SV MMX was well tolerated in this patient population, with the overall incidence of treatment-emergent adverse events generally similar to those of placebo and ciprofloxacin. Current evidence indicates that twice-daily rifamycin SV MMX is an effective and well tolerated treatment option for shortening the duration of non-dysenteric traveller's diarrhoea in adults."

Journal