LFF-571 / Novartis - LARVOL DELTA

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

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

Semi-synthesis of FK506 and GE2270 A analogues and their therapeutic applications (ACS-Fall 2022) - "Through late-stage functionalization and co-crystal structure-guided design, we identified a novel calcineurin-sparing analogue to improve the safety margin over FK506 and preserves renal function in animal models of acute kidney injury.Using co-crystal structure guided medicinal chemistry, semi-synthetic analogs of the natural product, GE2270 A, were designed, synthesized, and evaluated in animal models of infection. Chemistry efforts led to the clinical candidate, LFF571, evaluated for the treatment of C. difficile infections in humans."

Acute Kidney Injury • Infectious Disease • Nephrology • Oncology • Renal Disease

Investigational Treatment Agents for Recurrent Clostridioides difficile Infection (rCDI). (PubMed, J Exp Pharmacol) - "Updated CDI treatment guidelines suggest vancomycin and fidaxomicin as initial first-line therapies that have initial clinical cure rates of over 80%...Alternative treatments for rCDI include fecal microbiota transplant and a human monoclonal antibody, bezlotoxumab, that can be used in patients with high risk of rCDI. Various emerging potential therapies with narrow spectrum of activity and little systemic absorption that are in development include 1) Ibezapolstat (formerly ACX-362E), MGB-BP-3, and DS-2969b-targeting bacterial DNA replication, 2) CRS3213 (REP3123)-inhibiting toxin production and spore formation, 3) ramizol and ramoplanin-affecting bacterial cell wall, 4) LFF-571-blocking protein synthesis, 5) Alanyl-L-Glutamine (alanylglutamine)-inhibiting damage caused by C. difficile by protecting intestinal mucosa, and 6) DNV3837 (MCB3681)-prodrug consisting of an oxazolidinone-quinolone combination that converts to the active form DNV3681 that has activity in vitro..."

Journal • Review • Transplantation

Investigational drug therapies currently in early stage clinical development for the treatment of clostridioides (clostridium) difficile infection. (PubMed, Expert Opin Investig Drugs) - "These drugs include ACX-362E, DS-2969b, LFF 571, RBX2660, ribaxamase, ridinilazole that have advanced to at least phase 2 and several other drugs in phase 1 development. Expert Opinion: The challenge for these new agents is three-fold: 1) to have a novel approach such as a different target/mechanism of action; 2) be "significantly" better than existing agents in regard to "sustained clinical response"; or 3) be priced at a reasonable cost when it comes to market or perhaps all three. Their utility can only be proven by clinical trials."

Clinical • Journal • Review