DAV132 / Da Volterra - LARVOL DELTA

Antibiotic-related dysbiosis of gut microbiota in healthy volunteers: a comparative study of ceftazidime-avibactam, piperacillin-tazobactam, and ceftriaxone. (PubMed, Eur J Clin Microbiol Infect Dis) - "A previous published phase I study explored the role of a colon-targeted adsorbent DAV132 to mitigate the effects of antibiotics-related dysbiosis on the gut microbiota in healthy individuals. Consistent with beta diversity changes, bacterial interaction networks revealed greater and longer-lasting disruptions of bacterial interaction in the gut microbiota in the ceftriaxone group compared to the other two antibiotics. These findings highlight distinct patterns of microbiota disruption following ceftriaxone, ceftazidime-avibactam, and piperacillin-tazobactam treatments and underscore the importance of antibiotic selection in minimizing gut dysbiosis."

Journal • Gastrointestinal Disorder • Infectious Disease • Metabolic Disorders

DAV132 colon-targeted adsorbent prevents antibiotic-related dysbiosis in human volunteers and fecal microbiota transplantation mitigates anti-PD-1 resistance in avatar models (SITC 2024) - "*p < 0.05, * p < 0.01 Mann-Whitney U Tests. Statistics were performed on n = 10 mice"

Dysbiosis • IO biomarker • Oncology • CD8

The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers. (PubMed, Nat Commun) - "We conducted a randomized phase I study (EudraCT:2019-A00240-57) with 148 healthy volunteers (HV) to test two doses of DAV132, a colon-targeted adsorbent, alongside intravenous ceftazidime-avibactam (CZA), piperacillin-tazobactam (PTZ) or ceftriaxone (CRO) and a group without ATB. This effect was linked to activated CD8+ T cell populations in the tumor microenvironment. DAV132 represents a promising strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients."

Clinical • Journal • P1 data • Oncology • Transplantation

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

An obituary on DAV-132-authors' viewpoint on the current limits of pivotal trials in clinical microbiome research. (PubMed, J Antimicrob Chemother) - No abstract available

Journal

Prevention of antibiotic-induced dysbiosis in human volunteers by DAV132 and preservation of responsiveness to anti-PD-1 demonstrated by transplantation of human feces into tumor-bearing mice (AACR 2023) - "DAV prevented ATB-induced dysbiosis in HV treated with CZA or PTZ without influencing plasmatic concentrations. In avatar mice FMT from HV treated with CZA+DAV was able to preserve anti-PD-1 efficacy. These results provide rationale to launch clinical trials combining DAV in patients on ATB amenable to ICI."

Dysbiosis • Preclinical • Oncology • CD8

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