Ridinilazole resulted in a 53% relative risk reduction in recurrence of C. difficile infection compared to treatment with vancomycin
Ridinilazole preserved the gut microbiome compared to vancomycin: both in composition and diversity of the microbiome community
Ri-CoDIFy represents the largest and most comprehensive CDI assessment of the gut microbiome to date from over 600 CDI patients
Ridinilazole’s features are consistent with the principles of good antibiotic stewardship
Summit Therapeutics Inc. (NASDAQ:SMMT) (“Summit,” “we,” or the “Company”) and its product candidate, ridinilazole, today had an oral podium presentation at IDWeek 2022. IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP).
The oral presentation, entitled “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,” delivered by Dr. Pablo C. Okhuysen, M.D., Professor, Department of Infectious Diseases at MD Anderson Cancer Center, detailed the scientific data from the Ri-CoDIFy trial for our investigational, first-in-class antibiotic, ridinilazole, for the treatment of Clostridioides difficile infection (“C. diff. infection,” or “CDI”). There were 759 patients enrolled, with the mITT population comprising 745 patients; 323 were over the age of 65, 400 were hospitalized at the beginning of treatment, and 112 were previously diagnosed with COVID-19.
- Ridinilazole achieved a numerically higher sustained clinical response rate (73.0% vs 70.7%) than vancomycin, but did not achieve the pre-specified superiority endpoint
- Ridinilazole resulted in a 53% relative risk reduction in recurrence rates of C. diff. infection vs. vancomycin
- Recurrence of C. diff. infection is a major concern for patients with the disease; recurrence rates for infection in the United States are estimated to be approximately 20%-25% in patients after the initial treatment and with increased probabilities of recurrence after each subsequent episode i, ii
- Ridinilazole resulted in an 8.1% recurrence rate of CDI vs. 17.3% for patients treated with vancomycin
- Ridinilazole consistently resulted in decreased rates of recurrence compared to vancomycin in each of the prespecified subgroup analyses performed
- Patients with 10+ daily unformed bowel movements prior to treatment receiving ridinilazole experienced a disease recurrence rate of 5.8% as compared to 28.0% for vancomycin
- Patients, aged 65 or over experienced a 9.3% recurrence rate when treated with ridinilazole vs. 22.2% with vancomycin
- Patients with a prior COVID-19 diagnosis experienced recurrence 5.5% of the time when treated with ridinilazole vs. 24.6% when administered vancomycin
- Immunocompromised patients recurred 13.6% with ridinilazole vs. 26.3% with vancomycin
- Ri-CoDIFy is the largest and most comprehensive CDI assessment of the gut microbiome comprising over 600 CDI patients globally across different regions to date
- Patients treated with ridinilazole experienced a minimal impact on gut microbiome diversity compared to those patients treated with vancomycin
- Ridinilazole preserved the levels of protective secondary bile acids at the end of the treatment period, an important component of the microbiome, while vancomycin resulted in a substantial decrease in secondary bile acids
- Higher levels of secondary bile acids at the end of the treatment window are associated with earlier recovery of gut microbiome health and associated with a lower rate of recurrence of CDI
- Ridinilazole did not increase the gut resistome as evidenced by the relative lack of abundance of antibacterial resistance genes; exposure to vancomycin resulted in an expansion of the gut resistome
- Increases in the gut resistome are associated with an increased risk of resistance to antibiotics that a patient may be using or may use in the future
- Ridinilazole was well tolerated with a low rate of treatment discontinuation for adverse events in the Phase 3 study
“While both ridinilazole and vancomycin target Clostridioides difficile, the lower recurrence rates in those CDI patients treated with ridinilazole compared to that of vancomycin highlight the differing effects of the two drugs on the gut microbiome,” stated Dr. Pablo C. Okhuysen, the presenter of this data at IDWeek 2022. “Ridinilazole spared the gut microbiome and did not select for an increase in antimicrobial resistance at the end of treatment. Conversely, vancomycin decreased the microbiota diversity and selected for an increase of antimicrobial resistance to commonly-used antibiotics. The clinical and molecular results presented continue to validate the need to develop new antibiotics, that like ridinilazole, can selectively treat CDI (or for that matter, any infectious agent) while at the same time preserve microbiome diversity and not promote the emergence of antibiotic resistance. These features are consistent with the hallmark principles of antimicrobial stewardship and should be the focus of future anti-infective drug development.”
“We believe that this study may be indicative as to the need to change the way in which anti-infective agents are developed and assessed going forward, including the need for monitoring the impact of treatments on the gut microbiome,” added Robert W. Duggan, Chairman and Chief Executive Officer of Summit. “A diverse microbiome is critical to human health and protecting it must be a focus going forward. As we saw in the Ri-CoDIFy study, the health of the microbiome was associated with a lower rate of recurrence of CDI. I am very proud of the work of Team Summit in this significant breakthrough to the infectious disease space and beyond. As we have referenced several times and further illustrated by Drs. Giovanni, Schneider, Calder, and Fauci in the Journal of Infectious Diseases,iii the microbiome not only impacts infectious diseases, but can impact immune-mediated diseases and potentially beyond: maintaining a healthy, diverse microbiome is critical to maximizing patient safety and optimizing overall human health.”
A poster, entitled “A US-Based National Surveillance Study for the Susceptibility and Epidemiology of Clostridioides difficile Associated Diarrheal Isolates with Special Reference to Ridinilazole: 2020-2021″ is also available throughout IDWeek 2022.
Ridinilazole is not currently approved for use by any regulatory authority.
The presentation and poster are now available within the “Scientific Literature & Publications” section of our website: https://www.summittxinc.com/publications/.
Summit Therapeutics’ Mission Statement
To build a viable, long-lasting health care organization that assumes full responsibility for designing, developing, trial execution and enrollment, regulatory submission and approval, and successful commercialization of patient, physician, caregiver, and societal-friendly medicinal therapy intended to: improve quality of life, increase potential duration of life, and resolve serious medical healthcare needs. To identify and control promising product candidates based on exceptional scientific development and administrational expertise, develop our products in a rapid, cost-efficient manner, and to engage commercialization and/or development partners when appropriate.
We accomplish this by building a team of world class professional scientists and business administrators that apply their experience and knowledge to this mission. Team Summit exists to pose, strategize, and execute a path forward in medicinal therapeutic health care that places Summit in a well-deserved, top market share, leadership position. Team Summit assumes full responsibility for stimulating continuous expansion of knowledge, ability, capability, and well-being for all involved stakeholders and highly-valued shareholders.
