Tag Archives: Ridinilazole

Summit Announces Positive Data From Phase 2 C. difficile Clinical Trial Supporting Ridinilazole To Treat C. diffiicle Infection

SUMMIT ANNOUNCES POSITIVE TOP-LINE DATA FROM AN EXPLORATORY PHASE 2 CLINICAL TRIAL SUPPORTING RIDINILAZOLE AS A HIGHLY SELECTIVE ANTIBIOTIC FOR THE TREATMENT OF CDI

  • Ridinilazole treatment more preserving of gut microbiome than fidaxomicin

 * Listen In on September 26th 10aPT/1pET www.cdiffradio.com   live broadcast with our guests from Summit Therapeutics.

 

 

Oxford, UK, 5 September 2017Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM), the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (‘CDI’), today announces positive top-line data from an exploratory Phase 2 clinical trial that support ridinilazole as a highly selective and potent antibiotic product candidate for the treatment of CDI. In the Phase 2 clinical trial, ridinilazole preserved the gut microbiome of CDI patients to a greater extent than the marketed narrow-spectrum antibiotic, fidaxomicin. During the trial’s ten-day treatment period, ridinilazole treatment had markedly less impact on the gut microbiome of trial patients by measures of overall diversity and changes in key bacterial families, when compared to those trial patients dosed with fidaxomicin.

 

In the trial, ridinilazole and fidaxomicin both reduced the abundance of C. difficile. However, fidaxomicin-treated patients had reduced abundancy of other bacterial families associated with microbiome health. For a number of these bacterial families, the difference between the two treatments was statistically significant. Another measure of microbiome health is alpha diversity as measured by the Simpson’s Diversity Index. There was a greater reduction in alpha-diversity during fidaxomicin treatment compared with ridinilazole-treated patients. These measures were a key secondary endpoint of the clinical trial and provide additional evidence of ridinilazole’s precision in killing C. difficile while preserving the gut microbiome. The primary endpoint of the trial was safety, as measured by the number of treatment emergent adverse events and serious adverse events. During the trial, no new or unexpected safety signals were identified and ridinilazole was well-tolerated.

 

“We increasingly recognise the importance of a healthy and diverse gut microbiome for protection against recurrent CDI, which is a major challenge in the management of the disease. These latest clinical findings show ridinilazole better preserved the microbiome of CDI patients than fidaxomicin, the narrowest spectrum antibiotic currently available for CDI,” commented Professor Mark Wilcox, Consultant Microbiologist & Head of Microbiology Research & Development at the Leeds Teaching Hospitals NHS Trust, Professor of Medical Microbiology at the University of Leeds, and Public Health England’s Lead on C. difficile in England. “Further, these microbiome data are very supportive of ridinilazole’s profile as a highly selective antibiotic with the potential to achieve a meaningful improvement in clinical outcomes for CDI patients.”

 

The exploratory open-label Phase 2 clinical trial enrolled 27 patients aged between 18 and 90 years at trial sites in the US, the UK and the Czech Republic. Patients were randomly assigned to receive either ridinilazole (200mg, twice a day) or fidaxomicin (200mg, twice a day) for ten days. The trial population was unbalanced with more patients randomised to ridinilazole at higher risk of poorer clinical outcomes as measured by ATLAS score, and also with predisposing factors for recurrent CDI.

 

A secondary endpoint of sustained clinical response (‘SCR’), defined as clinical cure at the end of treatment and no recurrence of CDI within the next 30 days, was achieved in seven of 14 ridinilazole treated patients and six of 13 fidaxomicin treated patients. The trial was not designed for efficacy comparisons due to the small number of patients.

 

Dr David Roblin, Chief Medical and Operating Officer of Summit added, “Ridinilazole is a precision antibiotic that is designed to selectively target C. difficile while being highly preserving of the gut microbiome that plays a crucial role in naturally protecting against recurrent CDI. Ridinilazole has now provided evidence of its high selectivity in two complementary clinical trials. The data from our earlier Phase 2 trial showed a greater microbiome preservation of ridinilazole-treated patients compared with the current standard of care, vancomycin, which led to achieving statistical superiority in sustained clinical response. We believe ridinilazole has the potential to become a front-line therapy for CDI and look forward to initiating Phase 3 clinical trials in the first half of 2018.”

 

More detailed findings from this trial are expected to be presented at an upcoming international infectious disease conference. The results build on positive data from a Phase 2 proof of concept trial of ridinilazole that were published in The Lancet Infectious Diseases in April 2017. Ridinilazole is currently being prepared for Phase 3 clinical trials that are planned to commence in the first half of 2018.

 

SOURCE:  www.summitplc.com

Ridinilazole Compared With Vancomycin For Efficacy and Safety For Treatment of C. difficile Infection; A Phase 2 Randomized,Double-Blind,Active-Controlled,Non-Inferiority Study

Article Summary:

Background

Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.

Methods

We did a phase 2, randomized, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov, number NCT02092935.

Findings

Between June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation.

Interpretation

Ridinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted.

Funding

Wellcome Trust and Summit Therapeutics.

To read the article in its entirety, please click on the following link:

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30235-9/fulltext

Dr Richard J Vickers, PhD'Correspondence information about the author Dr Richard J Vickers
Glenn S Tillotson, PhD

,

Richard Nathan, MD

,

Sabine Hazan, MD

,

John Pullman, MD

,

Christopher Lucasti, DO

,

Kenneth Deck, MD

,

Prof Bruce Yacyshyn, MD

,

Benedict Maliakkal, MD

,

Yves Pesant, MD

,

Bina Tejura, MD

,

Prof David Roblin, FRCP

,

Prof Dale N Gerding, MD

,

Prof Mark H Wilcox, MD

for the

See appendix for full details of the CoDIFy study group
Published: 28 April 2017
Open Access Article has an altmetric score of 76

Open access funded by Wellcome Trust

Summit Therapeutics plc Outlines Phase 3 Program for Novel C. difficile Infection Antibiotic Ridinilazole

summit

Clostridium difficile Treatment – Phase 3 program outline —

 

SUMMIT OUTLINES PHASE 3 PROGRAMME FOR NOVEL CDI ANTIBIOTIC RIDINILAZOLE FOLLOWING FDA AND EMA REGULATORY MEETINGS

Oxford, UK, On 1 February 2017 – Summit Therapeutics plc
the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and C. difficile infection (‘CDI’),  outlines its Phase 3 programme for its novel antibiotic, ridinilazole, following recent regulatory meetings with the US Food and Drug Administration (‘FDA’) and European Medicines Agency (‘EMA’).

With input from the FDA and EMA, Summit intends to design the Phase 3 clinical programme to evaluate superiority of ridinilazole over standard of care in the treatment of C. diffiicle Infection (CDI).

A positive Phase 3 result on superiority has the potential to support the commercial launch of ridinilazole as a differentiated therapy that can both treat initial CDI and reduce disease recurrence.

Mr Glyn Edwards, Chief Executive Officer of Summit commented: “The constructive end of Phase 2 meetings with the US and European regulators have enabled us to design a Phase 3 programme that focuses on evaluating ridinilazole’s superiority over standard of care. This is something we believe would help differentiate our novel class antibiotic from currently marketed CDI treatments and those in late-stage development. Superiority in the combined measure of treatment of initial infection and importantly, reduction in recurrence, could position ridinilazole for front-line treatment of CDI.”
Summit discussed its Phase 3 development programme with the FDA at an End of Phase 2 meeting and through a scientific advice process with EMA. With input from both agencies, the Phase 3 programme is expected to include two trials evaluating ridinilazole as compared to the standard of care, vancomycin, each of which would enrol approximately 700 patients with CDI with the primary endpoint being superiority in sustained clinical response (‘SCR’). Other planned endpoints will include health economic outcome measures. The Phase 3 trial designs are consistent with the successful proof of concept Phase 2 trial, CoDIFy, in which ridinilazole achieved statistical superiority over vancomycin in SCR. SCR is a combined endpoint that measures cure at the end of treatment and a lack of recurrence in the 30 days after treatment. FDA also confirmed that ridinilazole would be eligible for Priority Review based on its QIDP designation.
Mr Edwards continued: “As we continue to evaluate our options to maximize the value of ridinilazole, our stronger financial position following the DMD programme partnership with Sarepta Therapeutics, Inc. means Summit has more time to fully explore all options. These include potentially entering into a collaboration with a third party or securing meaningful non-dilutive funding from government and charitable organizations. In parallel, activities

About Ridinilazole
Ridinilazole is an orally administered small molecule antibiotic that Summit is developing specifically for the treatment of CDI.

In preclinical efficacy studies, ridinilazole exhibited a narrow spectrum of activity and had a potent bactericidal effect against all clinical isolates of C. difficile tested. In a Phase 2 proof of concept trial in CDI patients, ridinilazole showed statistical superiority in sustained clinical response (‘SCR’) rates compared to the standard of care, vancomycin. In this trial, SCR was defined as clinical cure at end of treatment and no recurrence of CDI within 30 days of the end of therapy. Ridinilazole has received Qualified Infectious Disease Product (‘QIDP’) designation and has been granted Fast Track designation by the US Food and Drug Administration. The QIDP incentives are provided through the US GAIN Act and include an extension of marketing exclusivity for an additional five years upon FDA approval.

About Summit Therapeutics
Summit is a biopharmaceutical company focused on the discovery, development and commercialization of novel medicines for indications for which there are no existing or only inadequate therapies. Summit is conducting clinical programs focused on the genetic disease Duchenne muscular dystrophy and the infectious disease C. difficile infection.

Resources:

http://www.summitplc.com/media/press-releases/

July 5th Join C. diff. Spores and More With Dr. Garey and Dr. Vickers As We Discuss Summit Therapeutics: Ridinilazole, a Microbiome Preserving Antibiotic For the Treatment Of C. difficile Infection (CDI)

 

Listen to the live broadcast

on  July 5th,  2016

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Listen in to the live broadcast at 10a PT,   11a MT,   12p CT,   1p ET     6p UK


C. diff. Spores and More,”™ Global Broadcasting Network – innovative and educational interactive healthcare talk radio program discusses

This Episode:  

Summit Therapeutics: ridinilazole, a microbiome preserving antibiotic for the treatment of a C. difficile infection (CDI)

With Our Guests:

Dr. Kevin W. Garey; Chair, Department of Pharmacy Practice and Translational Research Professor of Pharmacy Practice at the University of Houston College of Pharmacy, Houston, TX

Dr. Richard Vickers, Chief Scientific Officer at Summit Therapeutics

Join us as we discuss a promising and new treatment for a C. difficile infection.  Summit Therapeutic’s Ridinilazole, a microbiome preserving antibiotic will be introduced with updates with our  guests Dr. Kevin W. Garey, Chair, Department of Pharmacy Practice and Translational Research, Professor of Pharmacy Practice at the University of Houston College of Pharmacy, Houston, Texas and  Dr. Richard Vickers, Chief Scientific Officer at Summit Therapeutics

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Through their interviews, the C Diff Foundation mission will connect, educate, and empower many worldwide.

Questions received through the show page portal will be reviewed and addressed  by the show’s Medical Correspondent, Dr. Fred Zar, MD, FACP,  Dr. Fred Zar is a Professor of Clinical Medicine, Vice HeZarPhotoWebsiteTop (2)ad for Education in the Department of Medicine, and Program Director of the Internal Medicine Residency at the University of Illinois at Chicago.  Over the last two decades he has been a pioneer in the study of the treatment of
Clostridium difficile disease and the need to stratify patients by disease severity.

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Summit Therapeutics Unveiled Findings From the Phase 2 CoDIFy Trial Featuring the Potential Of Ridinilazole In the Treatment Of C. diff. At ECCMID

In The News

Drug development company Summit Therapeutics PLC has presented positive results from a trial of its drug that combats hospital super-bug C.diff.

The company unveiled the findings from the Phase 2 CoDIFy trial highlighting the potential of ridinilazole in the treatment of Clostridium difficile (C.diff.)  infection at what is called a poster presentation, at the 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

Summit said the findings include a markedly reduced recurrence rate and a statistically superior rate of sustained clinical response in patients with CDI receiving ridinilazole, compared with those receiving the standard of care, vancomycin.

Sustained clinical response is defined as clinical cure at the end of treatment and no recurrence of the condition in 30 days after therapy.

Ridinilazole is a novel class antibiotic with the potential for broad use across the CDI disease spectrum. CDI is a serious threat in hospitals and care homes and there are between 450,000 and 700,000 cases in the US annually.

“Preventing disease recurrence is a major unmet need in CDI, both for newly diagnosed patients who are receiving initial treatment and for patients who are receiving treatment for recurrent disease,” said Dale Gerding, MD, Research Physician, Hines Veterans Affairs Hospital, Professor of Medicine, Loyola University Stritch School of Medicine, and an author on the presentation.

“In this context, it is very encouraging to see such a marked reduction in recurrences with ridinilazole in the Phase 2 trial,” Gerding said.

Glyn Edwards, chief executive of Summit, said: “Ridinilazole’s narrow spectrum of activity appeared to substantially reduce damage to the gut microbiome in the Phase 2 clinical trial, allowing patients to maintain or rebuild their natural defences against recurrence of CDI.”

Recurrence is a key problem as repeat episodes are typically more severe and associated with an increase in mortality rates and healthcare costs.

“The wealth of data we have reported on the compound to date, including the positive efficacy results presented today at ECCMID, suggest that ridinilazole could become a truly differentiated product with potential for broad use in CDI, including front-line treatment,” Edwards said.

Key efficacy findings from the trial presented at ECCMID were:

  • Statistical superiority in SCR with rates of 66.7% for ridinilazole compared to 42.4% for vancomycin
  • Marked reduction in recurrence with rates of 14.3% for ridinilazole compared to 34.8% for vancomycin
  • Cure rates at the end of treatment of 77.8% for ridinilazole and 69.7% for vancomycin

A copy of the poster is available from Summit’s web site .

 

To read this article in its entirety click on the following link:

http://www.proactiveinvestors.com/companies/news/124614/summit-therapeutics-plc-presents-positive-cdi-results-124614.html

 

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.

Summit Therapeutics Announces Additional Positive Data From the CoDIFy Phase 2 Clinical Trial That Show Narrow Spectrum Antibiotic ridinilazole Preserves Gut Microbiome in C.diff. Infection Patients

In The News *

Summit Therapeutics , the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (‘CDI’), announces additional positive data from the CoDIFy Phase 2 clinical trial that show the narrow spectrum antibiotic ridinilazole preserves the gut microbiome in CDI patients while the standard of care, vancomycin, inflicts substantial and long-lasting damage on the gut microbiome.

About Ridinilazole
Ridinilazole (SMT19969) is an orally administered small molecule antibiotic that Summit is developing specifically for the treatment of CDI. In preclinical efficacy studies, ridinilazole exhibited a narrow spectrum of activity and had a potent bactericidal effect against all clinical isolates of C. difficile tested. In a Phase 2 proof of concept trial in CDI patients, ridinilazole showed statistical superiority in sustained clinical response (‘SCR’) rates compared to the standard of care, vancomycin. In this trial, SCR was defined as clinical cure at end of treatment and no recurrence of CDI within 30 days of the end of therapy.  Ridinilazole has received Qualified Infectious Disease Product (‘QIDP’) designation and has been granted Fast Track status by the US Food and Drug Administration.  The QIDP incentives are provided through the US GAIN Act and include an extension of marketing exclusivity for an additional five years upon FDA approval.

“CDI results from damage to the microbiome, and patients experience further collateral damage through the use of broad spectrum antibiotics to treat CDI, leaving them vulnerable to recurrent disease,” commented David R. Snydman, MD, FACP, FIDSA, Chief, Division of Geographic Medicine and Infectious Diseases and Hospital Epidemiologist of Tufts University School of Medicine. “New, selective antibiotics are needed to minimise these high recurrence rates, and ridinilazole demonstrates an exceptional ability to preserve a patient’s microbiome and allow the growth of protective bacteria, which are vital to protecting against CDI.”

Preliminary analysis of these new data show ridinilazole to be highly preserving of the gut microbiome. Ridinilazole treated patients in CoDIFy exhibited no further damage to their microbiome during therapy with a proportion of patients showing initial evidence of recovery of key bacterial groups with roles in protecting from CDI. In stark contrast, vancomycin treated patients suffered substantial damage to their gut microbiome during treatment and this persisted in many patients during the 30-day post treatment period.

“These new results from the Phase 2 trial show ridinilazole preserves the patients’ microbiome while simultaneously working to eradicate the C. difficile bacteria. The clinical data strongly suggest that ridinilazole treatment may be better able to protect against recurrent disease than the current standard of care,” commented Glyn Edwards, Chief Executive Officer of Summit Therapeutics. “We believe this approach offers a clear advantage over conventional broad spectrum antibiotics currently used to treat CDI that cause substantial damage to the gut microbiome or approaches that aim to artificially re-establish a damaged gut microbiome following antibiotic treatment.”

“As evidenced by our growing body of clinical and preclinical data, we believe ridinilazole has the ideal profile to become a single therapeutic approach capable of both treating the initial infection and reducing the high rates of recurrent disease.”

These key microbiome findings strongly support recently reported results from the Phase 2 CoDIFy trial that showed ridinilazole to be statistically superior to vancomycin in sustained clinical response (‘SCR’), a combined endpoint capturing both initial cure and rates of recurrent CDI, with the improved SCR rate following ridinilazole treatment being driven by a large numerical reduction in recurrence. Full microbiome data are expected to be published at a scientific conference in due course.

About CoDIFy
CoDIFy was a double blind, randomized, active controlled, multi-centre, Phase 2 clinical trial that evaluated the efficacy of ridinilazole against vancomycin in a total of 100 patients. Half of the patients received ridinilazole for ten days (200 mg, twice a day), and the remaining half received vancomycin for ten days (125 mg, four times a day). The results of the trial showed ridinilazole achieved statistical superiority in SCR with rates of 66.7% compared to 42.4% for vancomycin.  SCR is defined as cure at the end of therapy and no recurrent disease 30 days post end of therapy. The primary analysis was conducted on the modified intent-to-treat (‘mITT’) population that comprised subjects with CDI confirmed by the presence of free toxin. These additional data on the preserving effect ridinilazole had on the gut microbiome support the top-line Phase 2 data and improvement observed in rates of recurrent disease.

 

About Ridinilazole
Ridinilazole (SMT19969) is an orally administered small molecule antibiotic that Summit is developing specifically for the treatment of CDI. In preclinical efficacy studies, ridinilazole exhibited a narrow spectrum of activity and had a potent bactericidal effect against all clinical isolates of C. difficile tested. In a Phase 2 proof of concept trial in CDI patients, ridinilazole showed statistical superiority in sustained clinical response (‘SCR’) rates compared to the standard of care, vancomycin. In this trial, SCR was defined as clinical cure at end of treatment and no recurrence of CDI within 30 days of the end of therapy.  Ridinilazole has received Qualified Infectious Disease Product (‘QIDP’) designation and has been granted Fast Track status by the US Food and Drug Administration.  The QIDP incentives are provided through the US GAIN Act and include an extension of marketing exclusivity for an additional five years upon FDA approval.

About Summit Therapeutics
Summit is a biopharmaceutical company focused on the discovery, development and commercialisation of novel medicines for indications for which there are no existing or only inadequate therapies. Summit is conducting clinical programs focused on the genetic disease Duchenne muscular dystrophy and the infectious disease C. difficile infection.

Further information is available at www.summitplc.com and Summit can be followed on Twitter (@summitplc).

To read the article in its entirety:

http://www.econotimes.com/Summit-Announces-Ridinilazole-Preserves-the-Gut-Microbiome-of-Patients-With-C-difficile-Infection-in-Phase-2-Trial-173750

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.

Summit Therapeutics Obtains Patent Protecting Its Novel Antibiotic Ridinilazole, A Treatment For C diff Infections (CDI)

IN THE NEWS **

Summit Therapeutics has won a key patent protecting its novel antibiotic, ridinilazole, for the treatment of infections caused by the Clostridium difficile hospital superbug.

The patent will grant Summit exclusivity in Europe for the use of ridinilazole in the treatment of CDI until at least 1 December 2029, following similar protection in other major markets, including the United States and Japan.

The patent grant and its emergence from a period of opposition meant it was now effective in all major markets.

Chief executive Glyn Edwards said: “The robust patent portfolio for ridinilazole, together with the strong Phase 2 clinical data showing statistical superiority over vancomycin, the current standard of care, further strengthens the potential commercial value of this novel product candidate in the treatment of CDI.”

With between 0.45m and 0.7m cases of CDI in the US annually, there remains great demand for better treatment of the infection.

Top-line results from a Phase 2 proof of concept trial reported in late 2015 showed that ridinilazole, an orally administered small molecule antibiotic, was statistically superior to vancomycin, the current standard of care, in the endpoint of sustained clinical response.

SCR was measured as cure at the end of treatment and no recurrence of CDI within 30 days of the end of treatment.

To read article in its entirety click on the following link:

 

http://www.digitallook.com/news/aim-bulletin/summit-therapeutics-gains-worldwide-patent-protection-for-c-diff-drug–1001525.html