VE303 / Vedanta Biosci - LARVOL DELTA

Safety and efficacy of a defined bacterial consortium, VE303, to treat HE. (PubMed, Hepatol Commun) - P2 | "VE303 was well tolerated in patients with cirrhosis and a history of overt HE, leading to the engraftment of certain VE303 strains and a higher percentage of patients with improved PHES."

Clinical • Journal • Fibrosis • Hepatology • Immunology

Vedanta Biosciences Publishes Additional Phase 2 VE303 Results in Nature Medicine (Businesswire) - P2 | N=79 | CONSORTIUM (NCT03788434) | Sponsor: Vedanta Biosciences, Inc. | "Vedanta Biosciences...today announced the publication of additional results from the Phase 2 CONSORTIUM study for its lead candidate, VE303, which is being evaluated for prevention of recurrent Clostridioides difficile infection (rCDI)...demonstrated that the higher dose of VE303 studied was well tolerated and reduced the odds of CDI recurrence by more than 80% compared with placebo....Results from the CONSORTIUM study informed the design and dose selection for the global, pivotal Phase 3 study, RESTORATiVE303, that is currently underway to confirm the efficacy and safety profile of VE303 in the prevention of rCDI. Topline data for this study are expected in 2026."

P2 data • P3 data: top line • Infectious Disease

Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection. (PubMed, Nat Med) - "VE303 potentiated early recovery of the host microbiome and metabolites with increases in short-chain fatty acids, secondary bile acids and bile salt hydrolase genes after antibiotic treatment for CDI, which is considered important to prevent CDI recurrences. These results support the idea that VE303 promotes efficacy in rCDI through multiple mechanisms."

Clinical • Journal • Infectious Disease

VE303. Vascular Surgery (ACS-CLINCON 2024) - No abstract available

Surgery

Fighting against Clostridioides difficile infection: Current medications. (PubMed, Int J Antimicrob Agents) - "Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and fecal microbiota transplantation (FMT) for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g., teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g., Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g., vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g., Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarizes current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation."

Journal • Review • Infectious Disease • Transplantation

RECOVERY OF MICROBIOME FUNCTIONAL PATHWAYS INVOLVED IN STICKLAND FERMENTATION IN PATIENTS RECEIVING VE303, A DEFINED BACTERIAL CONSORTIUM FOR CLOSTRIDIOIDES DIFFICILE INFECTION (CDI) (DDW 2024) - "Examination of the functional potential across assembled metagenomes suggests that VE303 colonization may contribute to recovery of the antibiotic-perturbed microbiome with diverse organisms that can reduce glycine and proline, and thus compete with C. difficile for nutrients associated with spore germination and outgrowth."

Clinical • Infectious Disease • Transplantation

A Comparison of Currently Available and Investigational Fecal Microbiota Transplant Products for Recurrent Clostridioides difficile Infection. (PubMed, Antibiotics (Basel)) - "This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Transplantation

RESTORATiVE303: VE303 for Prevention of Recurrent Clostridioides Difficile Infection (clinicaltrials.gov) - P3 | N=852 | Recruiting | Sponsor: Vedanta Biosciences, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease

VE303 for Treatment of Hepatic Encephalopathy (HE) (clinicaltrials.gov) - P2 | N=19 | Completed | Sponsor: Patricia Bloom | Active, not recruiting ➔ Completed

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

RESTORATiVE303: VE303 for Prevention of Recurrent Clostridioides Difficile Infection (clinicaltrials.gov) - P3 | N=852 | Not yet recruiting | Sponsor: Vedanta Biosciences, Inc.

New P3 trial • Infectious Disease

Update on Microbiota-derived therapies for recurrent Clostridioides difficile infections, 2023. (PubMed, Clin Microbiol Infect) - "Stool-derived products and bacterial consortia need to be clearly distinguished in terms of product characterization and their associated risks with specific long-term post-marketing evaluation similar to registries used for FMT. Their place in the therapeutic strategy for patients with rCDI requires further studies to determine the most appropriate patient population and administration route to prevent rCDI."

Journal • Review • Gastrointestinal Disorder • Infectious Disease • Transplantation

Review Article: Safety of Live Biotherapeutic Products Used for the Prevention of Clostridioides difficile Infection Recurrence. (PubMed, Clin Infect Dis) - "Requirements established by the FDA regarding the development of LBPs minimizes many of these prior concerns, and phase III trials have proven the safety and efficacy of 2 stool donor-derived LBPs: fecal microbiota, live-jslm (Rebyota™; formerly RBX2660) and fecal microbiota spores, live-brpk (Vowst™; formerly SER-109). Mild gastrointestinal side effects are common, but no severe drug-related adverse events have been reported with their use to date. A third LBP entering phase III clinical trials, VE303, follows a novel approach by sourcing bacterial strains from clonal cell banks and has demonstrated a similarly favorable safety profile."

Journal • Review • Gastrointestinal Disorder • Infectious Disease

TRIAL OF A DEFINED BACTERIAL CONSORTIUM, VE303, TO TREAT HEPATIC ENCEPHALOPATHY (AASLD 2023) - P2 | "Eligible patients were taking lactulose and rifaximin, no recent systemic antibiotics, and had MELD <20... Of 19 patients enrolled, 1 withdrew prior to receiving vancomycin, and the remaining 18 patients completed study drug and were followed for 6 months... VE303 was safe, led to certain strain engraftment, and a higher percentage with improved psychometric HE scores in patients with a history of overt HE. A larger trial to verify these findings and to determine patient subgroups most likely to benefit is warranted."

Late-breaking abstract • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

VE303. Vascular Surgery (ACS-CLINCON 2023) - "DESCRIPTION All presentation times are approximate."

Surgery

Biological Features of Response to VE303, a Defined Bacterial Consortium, in Patients with Clostridioides difficile Infection (CDI): Results from the Phase 2 CONSORTIUM Study (IDWeek 2023) - No abstract available

Clinical • P2 data • Infectious Disease

Recurrent Clostridioides difficile Infection: Current Clinical Management and Microbiome-Based Therapies. (PubMed, BioDrugs) - "Fecal microbiota transplantation in recurrent C. difficile infection has demonstrated higher success rates than vancomycin, fidaxomicin, or placebo...In the ECOSPOR III trial of SER-109, an oral formulation of bacterial spores, a significant reduction in the recurrence rate (12%) was observed compared with placebo (40%). In the phase III PUNCH CD3 trial, RBX2660 also demonstrated high efficacy rates of 70.6% versus 57.5%...Other standardized microbiome-based therapies currently in the pipeline are VE303, RBX7455, and MET-2. Antibiotic neutralization strategies, vaccines, passive monoclonal antibodies, and drug repurposing are other therapeutic strategies being explored to treat C. difficile infection."

Journal • Review • Infectious Disease • Transplantation

PHARMACODYNAMIC RESPONSE TO A DEFINED BACTERIAL CONSORTIUM, VE303, IN PATIENTS WITH CLOSTRIDIOIDES DIFFICILE INFECTION (CDI): RESULTS OF THE PHASE 2 CONSORTIUM STUDY (DDW 2023) - "In subjects at high risk of rCDI, VE303 species were positively correlated with beneficial Clostridia , short-chain fatty acids, and UDCA, and negatively correlated with recurrence-associated Proteobacteria. VE303 may protect against rCDI through a combination of direct exposure to the consortium strains and VE303-mediated recovery of the endogenous microbiota and metabolites."

Clinical • P2 data • PK/PD data • Infectious Disease • Transplantation

PureTech Founded Entity Vedanta Biosciences Receives Fast Track Designation for VE303 and Presents Phase 2 Data at Digestive Disease Week (Businesswire) - "PureTech Health plc...noted today that its Founded Entity, Vedanta Biosciences, a clinical-stage company that is developing a potential new category of oral therapies based on defined bacterial consortia, announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation to Vedanta’s defined bacterial consortium candidate, VE303, for the prevention of recurrent Clostridioides difficile infection (rCDI). Fast Track designation is a process designed to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need."

Fast track designation • Infectious Disease

VE303, a Defined Bacterial Consortium, for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial. (PubMed, JAMA) - P2 | "A larger, phase 3 study is needed to confirm these findings. ClinicalTrials.gov Identifier: NCT03788434."

Clinical • Journal • Infectious Disease

"هل من الممكن استخدام البكتيريا لمحاربة البكتيريا ؟ يعني نخلي الأمور تقبس بينهم والبشر هم المستفيدين ! في دراسة حديثة استخدم VE303 هو مرشح كونسورتيوم بكتيري يعطى عن طريق الفم ومصمم بصورة محددة لمحاربة العدوى الكلوستيريديوم العسيرة عالية الخطورة (CDI). يتكون VE303 من 8 أنواع… https://t.co/eiIyShIcNI" (@ahakawi)

VE303 for Treatment of Hepatic Encephalopathy (HE) (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: Patricia Bloom | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis

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

The Urgent Threat of Clostridioides difficile Infection: A Glimpse of the Drugs of the Future, with Related Patents and Prospects. (PubMed, Biomedicines) - "Many possible drugs of the future for CDI, with diverse mechanisms of action, are in development in the form of microbiota-modulating agents (e.g., ADS024, CP101, RBX2660, RBX7455, SYN-004, SER-109, VE303, DAV132, MET-2, and BB128), small molecules (e.g., ridinilazole, ibezapolstat, CRS3123, DNV3837, MGB-BP-3, alanyl-L-glutamine, and TNP-2198), antibodies (e.g., IM-01 and LMN-201), and non-toxic strains of CD (e.g., NTCD-M3). The development of some therapeutic agents (e.g., DS-2969b, OPS-2071, cadazolid, misoprostol, ramoplanin, KB109, LFF571, and Ramizol) stopped due to failed clinical trials or unknown reasons...The current pipeline of anti-CDI medications appears promising. However, it will be fascinating to see how many of the cited are successful in gaining approval from drug regulators such as the US FDA and becoming medicines for CDI and r-CDI."

Journal • Review • Developmental Disorders • Infectious Disease

VE303 for Treatment of Hepatic Encephalopathy (HE) (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Patricia Bloom | Trial completion date: Jun 2023 ➔ Sep 2023 | Trial primary completion date: Dec 2022 ➔ Mar 2023

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

"Microbiota based live biotherapies are promising - RBX2660 (PUNCH-CD3 trial) - SER-109 (ECOSPOR-III trail) - CP101 (PRISM3 trial) - VE303 (CONSORTIUM trial) #IDweek2022" (@AlaaAtamna)

Infectious Disease