Slide 1: Ri-CoDIFy - A Phase 3 Study of Ridinilazole Compared with Vancomycin for CDI
IDWeek 2022 Ri-CoDIFy - 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 Pablo C. Okhuysen, M.D., FACP, FIDSA1; Mayur S. Ramesh, M.D.2; Thomas J. Louie, M.D., FRCPC3; Richard
Slide 2: Disclosure Statement
Disclosure Statement Pablo C. Okhuysen, MD has faculty grant/research support from Merck Sharp and Dohme Corp, Deinove, Summit, Melinta and Napo. He is a paid consultant to Napo and is a consultant with Ferring Pharmaceuticals, Inc. 2 Ridinilazole is an investigational therapy and is not approved by
Slide 3: Clostridioides difficile infection (CDI) is a public health threat
Clostridioides difficile infection (CDI) is a public health threat • Primary and recurrent Clostridioides difficile infection (rCDI) are a significant financial and medical burden to patients and health care institutions1 • Agents that selectively treat primary CDI and prevent rCDI are needed2,3 • F
Slide 4: Ri-CoDIFy 1 and 2: Phase III Study Design
Ri-CoDIFy 1 and 2: Phase III Study Design NCT03595553 and NCT03595566 Combined global, randomized, double-blind, active controlled, parallel group, study to compare the efficacy of ridinilazole with vancomycin for the treatment of C. difficile infection (CDI). Primary Endpoint: Ridinilazole • Sustai
Slide 5: Ri-CoDIFy - Baseline Characteristics (N=745)
Ri-CoDIFy - Baseline Characteristics (N=745) mITT Population Ridinilazole (N=370) Vancomycin (N=375) n (%) n (%) Age (Years) – Median 61.0 63.0 ≥ 65 161 (43.5) 162 (43.2) Gender – Female 209 (56.5) 227 (60.5) Race – White 333 (90.0) 331 (88.3) Region US/Canada 93 (25.1) 104 (27.7) Europe 229 (61.9)
Slide 6: Ri-CoDIFy Response Rates (%)
Ri-CoDIFy Response Rates (%) mITT Population Ridinilazole achieved a numerically higher SCR rate than vancomycin, but did not meet superiority 92.3 86.5 73 70.7 Patients (%) Ridinilazole (N=370) Vancomycin (N=375) 17.3 8.1 SCR Clinical Response Recurrence Rate at 30 days post EOT at EOT + 2 days Rid
Slide 7: Ri-CoDIFy Recurrence
Ri-CoDIFy Recurrence Recurrence Rate: Ridinilazole 8.1% (30/370) vs vancomycin 17.3% (65/375); Difference -9.2 (95% CI -14.1, -4.5; p = 0.0002) Ridinilazole’s absolute risk reduction of -9.2% resulted in a 53% relative risk reduction in recurrence rate compared to vancomycin Time to Recurrence Ridin
Slide 8: Recurrence Rates
Recurrence Rates Key Subgroup analyses showed consistent reduction in recurrence rate for ridinilazole % Recurrence Rate Ridinilazole Vancomycin 28 26.3 24.6 22.2 21.2 21 19.4 19.3 19.2 15.1 14.3 13.6 13.6 14.0 13.6 11.3 10.5 11.3 9.3 8.8 7.2 5.8 5.5 6.1 Age >=65 UBMs >=10 >= 1 Prior Severe Disease
Slide 9: Microbiome Alpha Diversity and Relative Abundance of Phyla
Microbiome Alpha Diversity and Relative Abundance of Phyla Shotgun metagenomic analysis of fecal microbiome (N=608) P = 0.4748 P < 0.0001 P = 0.0004 Ridinilazole Vancomycin * * * # 3 # 19% 13% # # Phylum 2 19% 20% 31% # Shannon Index # Other Actinobacteria Bacteroidetes 64%# 61%# 38% Firmicutes Prot
Slide 10: Microbiome Beta Diversity
Microbiome Beta Diversity Shotgun metagenomic analysis of fecal microbiome Ridinilazole minimally impacted the baseline microbiota community structure compared to vancomycin at EOT. Jaccard Distance Bray-Curtis Dissimilarity BSL = baseline PCo1 = principal coordinate 1 EOT = end of treatment PCo2 =
Slide 11: Microbiome Derived Secondary Bile Acids
Microbiome Derived Secondary Bile Acids • At EOT ridinilazole preserved the levels of protective secondary bile acids (SBA) and vancomycin treatment resulted in a substantial decrease in SBA. • Higher levels of SBA at EOT are associated with higher rates of SCR in all patients in combined treatment
Slide 12: Impact of CDI Treatment on the Gut Resistome
Impact of CDI Treatment on the Gut Resistome Shotgun metagenomic analysis of fecal microbiome • Ridinilazole did not increase the gut resistome as evidenced by the relative abundance of antibacterial resistance genes • Vancomycin exposure resulted in an expansion of the gut resistome at EOT Third Ge
Slide 13: Sub-Population of Patients with a More Intact Gut Microbiome at Baseline
Sub-Population of Patients with a More Intact Gut Microbiome at Baseline 70% of patients in the study Baseline Median Secondary Bile • Sub-population with a more intact microbiome, defined as patients not Acid Relative Abundance receiving antibiotics at baseline, is biologically different (greater s
Slide 14: Overall Summary of Adverse Events
Overall Summary of Adverse Events Safety population Ridinilazole (N=374) Vancomycin (N=377) n (%) n (%) TEAEs by Severity Mild 69 (18.4) 73 (19.4) Moderate 44 (11.8) 40 (10.6) The most common TEAEs included: Severe 23 (6.1) 21 (5.6) Ridinilazole Vancomycin Related TEAEs by Severity Diarrhea 5.6% 3.7
Slide 15: Ri-CoDIFy Phase 3 Study Summary
Ri-CoDIFy Phase 3 Study Summary • Treatment with ridinilazole resulted in a numerically higher sustained clinical response rate vs vancomycin but did not meet the study’s prespecified superiority threshold. • Treatment with ridinilazole resulted in a 53% relative risk reduction in recurrence compare
Slide 16: Acknowledgements
Acknowledgements We are grateful to the patients and their care givers, to investigators and all site staff who participated in the Ri-CoDIFy study. This study was partly supported by the Biomedical Advanced Research and Development Authority (BARDA). Contact info: Pablo C. Okhuysen pcokhuysen@mdand