ridinilazole (SMT 19969) / Summit Therapeutics, Eurofarma - LARVOL DELTA

Some Newer Antibiotics Active Against Helicobacter pylori and Anaerobic Bacteria and the Potential Benefits of Their Wider Availability in More Countries: A Narrative Review. (PubMed, Antibiotics (Basel)) - "Given the limited number of antibiotics for treating CDI and fidaxomicin nonavailability in many countries, it is necessary to conduct more extensive laboratory and clinical studies of promising antibiotics such as ibezapolstat, delafloxacin, lascufloxacin, omadacycline, eravacycline, ridinilazole, and CRS3123...Research on rifasutenizol for bacterial vaginosis, sarecycline and nadifloxacin for acne vulgaris and amixicile for periodontal diseases needs to be expanded. For H. pylori infection, delafloxacin, sitafloxacin, nemonoxacin, zoliflodacin, and rifasutenizol may improve the suboptimal success of most eradication regimens...Establishing more research groups, careful examination of market issues, and additional approaches, such as nanomaterials, efflux pump inhibitors, phage therapy, and CRISPR-Cas systems, should be beneficial. Notwithstanding the difficulties, there are many opportunities to promote research on and potential use of newer antibiotics which show..."

Journal • Review • Acne Vulgaris • Dental Disorders • Dermatology • Infectious Disease • Periodontitis • Vaginitis

Public contributions to the development of antibiotics: two successful and two failed investments. (PubMed, J Pharm Policy Pract) - "The aim is to showcase a detailed analysis of the contribution of public funding to two successful (gepotidacin and zoliflodacin) and two failed (epetraborole and ridnilazole) public sector investments in antibiotic development, using a previously developed and refined framework...Whilst the two unsuccessful antibiotics received considerably smaller sums from public or philanthropic sources ($85 million for ridinilazole and $18 million for epetraborole)...However, there is a significant amount of missing funds-related information. The work we have done on identifying sources for funding can be referenced in support pharmaceutical price negotiations to better reflect the level of public contribution to product development."

Journal

Viologen Covalent Organic Frameworks Integrating Synergistic Singlet and Triplet Excitation for Efficient Photosynthesis of Benzazole Pharmaceuticals. (PubMed, Angew Chem Int Ed Engl) - "More impressively, PyBpy-3,3'-ion serves as an outstanding photocatalyst for the facile and highly efficient syntheses of over 10 key benzazole pharmaceuticals, such as Ridinilazole, PMX-610, Tafamidis, and so on, as well as the gram-scale preparation of Thiabendazole and Pimobendan under mild conditions. Our work establishes a rational design protocol to achieve the synergistic S1 and T1 excitation in viologen for highly efficient photocatalytic synthesis of high-value pharmaceuticals."

Journal

Repurposing of the bisbenzimide antibiotic Ridinilazole as an antiviral compound against human cytomegalovirus. (PubMed, J Gen Virol) - "Western blotting and electron microscopy revealed that Ridinilazole had no obvious effect on HCMV protein production, but did decrease the number of HCMV capsids in the cytoplasm. Overall, we identified an antibiotic compound previously used in humans that could be repurposed as an antiviral compound to efficaciously inhibit replication of HCMV."

Journal • Cytomegalovirus Infection • Herpes Simplex • Infectious Disease • Influenza • Respiratory Diseases

Repurposing antibacterial drugs identifies ridinilazole and CRS3123 as promising candidates against vancomycin-resistant enterococci. (PubMed, Sci Rep) - "In vivo studies using the C. elegans model confirmed potent efficacy, with CRS3123 reducing both E. faecium and E. faecalis burden similar to linezolid while ridinilazole were effective against E. faecium only. These findings support ridinilazole and CRS3123 as promising candidates for further VRE therapeutic development."

Journal

Comparative Efficacy of Antibiotic Treatments for Clostridioides difficile Infection: A Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Introduction: Clostridium difficile infection (CDI) remains a major contributor to hospital-acquired diarrhea, associated with significant morbidity, high recurrence rates, and substantial healthcare costs. The meta-analysis included four randomized controlled trials, encompassing a total of 1,368 patients. In terms of clinical cure, the results indicated no statistically significant difference between vancomycin and fidaxomicin or other emerging antibiotic agents, with an odds ratio (OR) of 1.03 (95% confidence interval [CI]: 0.78–1.35; I² = 76%). However, when evaluating recurrence rates, fidaxomicin and other novel therapies demonstrated a significantly greater reduction in recurrence compared to vancomycin, with an OR of 0.46 (95% CI: 0.33–0.64; I² = 44%). While clinical cure rates were comparable between fidaxomicin and vancomycin, fidaxomicin was more effective in preventing CDI recurrence, suggesting its potential benefit in high-risk patient populations."

Retrospective data • Infectious Disease

New investigational agents for the treatment of clostridioides difficile infections. (PubMed, Expert Opin Investig Drugs) - "Ibezapolstat, CRS3123, and ridinilazole were identified with unique mechanisms of action and narrow spectrums of activity that result in gut microbiome preservation and reduced recurrent CDI (rCDI) rates...Some have the ability to restore the microbiome (VE303) or preserve intestinal integrity (e.g. REC-3964, LMN-201, AQ)...CDI is a significant burden to the healthcare system and the quality of life for patients who suffer from CDI and rCDI. Further development of these investigational agents to prevent this cycle are of upmost importance."

Journal • Review • Infectious Disease

In vitro susceptibility of clinical Clostridioides difficile isolates in Israel to metronidazole, vancomycin, fidaxomicin, ridinilazole and ibezapolstat. (PubMed, BMC Gastroenterol) - "RDZ and IBZ demonstrated potent in vitro activity against 313 C. difficile isolates belonging to different STs. These two antimicrobials may serve as effective agents for C. difficile infection."

Journal • Preclinical • Infectious Disease

Comparative effectiveness of different therapies for Clostridioides difficile infection in adults: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, Lancet Reg Health Eur) - "In recurrent cases, fidaxomicin (P-score: 0.6734) showed significantly greater effectiveness than vancomycin (P-score: 0.3677) and tolevamer (P-score: 0.0365). For non-recurrent CDI treatments ridinilazole, fidaxomicin, FMT and nitazoxanide were equally effective...Our findings suggest that the preventive use of probiotics might be questioned. None."

HEOR • Journal • Retrospective data • Infectious Disease • 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

A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response. (PubMed, Clin Infect Dis) - P3 | "Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566."

Clinical • Clinical data • Journal • P3 data • Infectious Disease

Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis. (PubMed, Tech Coloproctol) - "Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics."

Clinical • Journal • Retrospective data • Review • Infectious Disease

A US-based national surveillance study for the susceptibility and epidemiology of Clostridioides difficile isolates with special reference to ridinilazole: 2020-2021. (PubMed, Antimicrob Agents Chemother) - "In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]...Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype."

Journal

Clostridioides difficile resistance to antibiotics, including post-COVID-19 data. (PubMed, Expert Rev Clin Pharmacol) - "The mean resistance to 2 mg/l vancomycin, 2 mg/l metronidazole, 4 mg/l moxifloxacin, and 4 mg/l clindamycin was 4.7% (0 to ≥ 26% in two studies), 2.6% (0 to ≥ 40% in 3 studies), 34.9% (6.6->80%), and 61.0% (30->90%), respectively. Resistance to erythromycin (>60-88%), rifampin (>23-55.0%), imipenem (0.6 to > 78% in a clone), tigecycline (0-<5.0%), and fidaxomicin (0-2%) was also found...New approaches, including biotherapeutics (Rebyota), strains, antibiotics (ridinilazole and ibezapolstat), and monoclonal antibodies/cocktails merit further evaluation...Post-COVID-19 resistance should be separately presented. Some discrepancies between vancomycin and metronidazole results need to be clarified."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

Clostridioides difficile - New Insights and Therapy Recommendations (PubMed, Dtsch Med Wochenschr) - "The updated 2021 ESCMID guidelines recommend fidaxomicin instead of vancomycin as the antibiotic of choice for the treatment of CDI because of its lower recurrence rate...In the future, ridinilazole may be available as another therapeutic option that has a narrow spectrum of activity and low intestinal absorption. For the treatment of recurrent CDI, the new guidelines also include the use of the monoclonal antibody bezlotoxumab. In addition, a new oral microbiome therapy, SER-109 (capsules containing purified Firmicutes spores), which showed promising results in a phase 3 study, may provide an easy-to-administer alternative to fecal microbiota transplantation. Hopes for a well-performing toxoid vaccine for primary and secondary prevention of CDI have unfortunately not been fulfilled in the CLOVER trial."

Journal • Infectious Disease • Transplantation

The Novel DNA Binding Mechanism of Ridinilazole, a Precision Clostridiodes difficile Antibiotic. (PubMed, Antimicrob Agents Chemother) - "DNA binding and genomic localization was confirmed through confocal microscopy utilizing the intrinsic fluorescence of ridinilazole upon DNA binding. As such, ridinilazole has the potential to be the first antibiotic approved with a DNA minor groove binding mechanism of action."

Journal • Infectious Disease

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

Ri-CoDIFy 1: Comparison of Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection (clinicaltrials.gov) - P3 | N=759 | Completed | Sponsor: Summit Therapeutics | N=355 ➔ 759

Enrollment change • Infectious Disease

Emerging Options for the Prevention and Management of Clostridioides difficile Infection. (PubMed, Drugs) - "These agents include one antibiotic (ridinilazole), three live biotherapeutic products (LBPs) (CP101, RBX2660, and SER109), and two toxoid vaccines (PF06425090 and a second toxoid vaccine). As new prevention and treatment strategies enter the market, clinicians and administrators will need knowledge of these products to make rational decisions on how best to adopt them into clinical practice."

Journal • Infectious Disease

Ri-CoDIFy 3: Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent Subjects (clinicaltrials.gov) - P3 | N=2 | Terminated | Sponsor: Summit Therapeutics | N=40 ➔ 2 | Trial completion date: Dec 2023 ➔ Sep 2022 | Recruiting ➔ Terminated; SMT19969-C006 study was terminated in alignment with corporate decision to pursue further development of drug candidate with a partner.

Enrollment change • Trial completion date • Trial termination • Infectious Disease

A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Ridinilazole Compared with Vancomycin for the Treatment of Clostridioides difficile Infection (IDWeek 2022) - No abstract available

Clinical • P3 data • Infectious Disease

A US Based National Surveillance Study for the Susceptibility and Epidemiology of Clostridioides difficile Associated Diarrheal Isolates with Special Reference to Ridinilazole: 2020-2021 (IDWeek 2022) - No abstract available

Clinical • Infectious Disease

Transcriptomic analysis of the Clostridioides difficile-targeting antimicrobial ridinilazole implicates disruption of energy-generation pathways as its mechanism of action (ECCMID 2022) - No abstract available

Symmetric bis-benzimidazoles as DNA minor groove-binding agents with anti-tumour and antibacterial activity, and the evolution of the drug ridinilazole for the treatment of CLOSTRIDIUM difficile infections. (PubMed, Bioorg Med Chem) - "One of these BBZs has specific activity against Clostridium difficile and is currently in a phase 3 clinical evaluation as the drug ridinilazole. X-ray and computer modelling studies showed that BBZs typically exhibit high specificity for oligonucleotide sequences that occur in the minor groove of DNA."

Journal • Review • Infectious Disease • Oncology

Ridinilazole: a novel, narrow-spectrum antimicrobial agent targeting Clostridium (Clostridioides) difficile. (PubMed, Lett Appl Microbiol) - "One such agent, fidaxomicin, has been in therapeutic use for several years and is now recommended as a first-line treatment for CDI, as it is superior to vancomycin in reducing risk of recurrence. Phase I and II clinical trials have been completed, with ridinilazole showing high tolerability and efficacy in treatment of CDI, and superiority over vancomycin in reducing recurrence of CDI within 30 days of treatment completion. Phase III trials are currently underway, the results of which may prove its potential to reduce recurrent CDI and lessen the heavy health and financial burden C. difficile imposes on patients and healthcare systems."

Journal • Review • Infectious Disease