Benzinga | Dec 20, 2021 08:35AM EST

Summit Therapeutics Announces Topline Results For Phase III Ri-CoDIFy Study For C. Difficile Infection; Says Ri-CoDIFy Did Not Meet Primary Endpoint

Summit Therapeutics Inc. (NASDAQ:SMMT) ("Summit" or the "Company") today announced topline results for the Phase III Ri-CoDIFy study evaluating its investigational drug, ridinilazole, for the treatment of and Sustained Clinical Response (SCR) for patients suffering from C. difficile infection (C. diff. infection or CDI). The study showed that ridinilazole resulted in a higher observed SCR rate than vancomycin but did not meet the study's primary endpoint for superiority. SCR is defined as Clinical Response of the treated episode of CDI and no recurrence of the infection through 30 days after the end of treatment.

Patients treated with ridinilazole, a precision antibiotic, experienced substantially less recurrence of C. diff. infection as compared to patients administered vancomycin (nominal p-value = 0.0002). Recurrence, for purposes of the Ri-CoDIFy study, is defined as a new episode of diarrhea (?3 unformed bowel movements) in a 1-day period with a positive C. difficile test that requires CDI antimicrobial treatment in subjects who achieved Clinical Response. Particularly promising results were identified in patients who were considered high-risk, including those considered immunocompromised or with a history of COVID-19 infection.

"Reduced recurrence rates are very consistent with our Phase II data and the mechanism of action of this drug," said Dr. Fong Clow, Head of Biometrics at Summit. "Although Ri-CoDIFy did not meet the primary endpoint for the design of this study, we did see a meaningful reduction in recurrence in the ridinilazole arm, which we believe is tied to the precision properties of ridinilazole and its associated relative sparing of the gut microbiome. We believe this is a viable measurement of the effect of this drug and has biological significance as to the potential value of the drug. It is essential that we consider the value of recurrence, the impact on the microbiome, and the measurement of this biological outcome when considering the value of a drug like ridinilazole and its potential benefits to the patient and human health."

"We believe this study was indicative of worthwhile work, as the knowledge that we have acquired as a team over the past 18 months is priceless," said Robert W. Duggan, Chairman and Chief Executive Officer of Summit. "The differences between episodes of recurrence experienced by patients in the two arms of this study may be indicative as to the significance of precision medicinal therapies that spare the microbiome from damage. A balanced microbiome is critical to human health and protecting it must be a focus going forward for medicinal therapies whose desire is to maximize patient safety and optimize human health: I believe the impact on a balanced microbiome is a critical component of the evaluation of any drug and will become an essential part of evaluating drug safety and efficacy as we move forward in time. Dysbiosis of the microbiome can lead to recurrence when treating CDI, as we believe the differences in recurrence rates between the two arms of the study indicate, but also may increase the risk of other immune-mediated and infectious diseases, such as COVID-19.1 The opportunity for medicinal therapies to leverage the microbiome to improve the quality of life from newborns to the last days of life is an opportunity worth taking seriously. Team Summit fully anticipates playing a meaningful role in this opportunity to improve the quality of human life."

"I am excited to continue to learn more about ridinilazole's potential merits for its treatment of CDI patients," added Dr. Danelle James, Head of Clinical Development and Medical Affairs at Summit. "The recurrence rates, a clinically meaningful outcome, with ridinilazole was substantially lower than vancomycin -- a likely outcome of ridinilazole's highly-selective nature. We believe that high-risk patient populations -- those considered immunocompromised and those with a history of COVID-19 -- are more likely to be harmed by an increased level of dysbiosis of the gut microbiome, and dysbiosis has a greater impact to their overall health. Innovating the way in which we treat C. difficile infection via new mechanism, precision antibiotics could add value to not only patients suffering from CDI by reducing disease recurrence, but also help in the fight against antimicrobial resistance, a paradigm that is foundational for antibiotic drug stewardship."

"We would like to extend our true gratitude to all of those who supported our efforts in the discovery, research, and clinical development of ridinilazole, helping show the potential value of ridinilazole to patients, providers, and the healthcare ecosystem," added Dr. Maky Zanganeh, Chief Operating Officer, and a member of Summit's Board of Directors. "The patients who participated in our clinical trials, along with their families and caregivers, are an integral part of the journey towards achieving our goal of improving overall human health. To our study investigators, we are truly appreciative of your trust in Team Summit and ridinilazole, as well as your unparalleled care of the patients in our trial and your drive to resolve serious unmet medical needs. Finally, we would like to extend a sincere appreciation to those organizations, including BARDA, who continue to provide invaluable support in developing ridinilazole."

Full results from the Ri-CoDIFy study will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. We will continue to evaluate the underlying data and perform additional analyses, including analyses specific to the microbiome, in order to discuss our complete package with the regulatory agencies. The use of ridinilazole is not approved and its safety and efficacy have not been evaluated by regulatory authorities, including the FDA.