Impact case study database

C. difficile (C. diff) infections are a major problem; in 2015-16 in the UK alone, there were 5,200 cases in hospitals and more than 14,000 in primary care institutions. It is estimated that there are more than 1,000,000 cases in the US and Europe each year. This anaerobic bacterium usually affects patients with pneumonia or cancer who have been treated with broad spectrum antibiotics (especially cephalosporins) which have destroyed their natural gut flora. Although there are two drugs (metronidazole and vancomycin) that are currently partially effective, C. diff infections still cause >30,000 deaths annually in the USA and >10,000 in Western Europe each year. The economic cost of C. diff infection is significant, with one study estimating annual acute care costs at USD4,800,000,000 in the USA. New therapies are thus desperately needed.

The new antibiotic Ridinilazole, which has grown directly from the invention of the BBZ series of compounds by Mann and Neidle, is such a drug. Ridinilazole is structurally very closely related to the original BBZ compounds invented by Stephen Neidle and John Mann (see structures above), and represents a fundamental repositioning of particular BBZ compounds from generalised cell proliferation inhibitors to targeted anti-infective agents. The impact which has grown from Mann’s original synthetic work and subsequent collaboration with Summit Therapeutics is that a major new drug has been developed and within the current REF period has been advanced through Phase 2 clinical trials, attracted significant support and recognition from the US Food and Drug Administration and Department of Health and Human Services and is now well through Phase 3 clinical trials.

Development of Ridinilazole is a major programme for Summit Therapeutics [E1, E2]. Phase I clinical evaluation was highly successful. Owing to its highly targeted spectrum of activity and ability to spare the normal gut microbiota, Ridinilazole was found to provide significant advantages over metronidazole and vancomycin, the mainstay antibiotics for C. diff infections (CDI). In addition, oral ridinilazole is well tolerated and exhibits a prolonged post-antibiotic effect [E3].

Phase 2 (2014 – 2016) clinical evaluation at hospitals in the USA and Canada was completed with a strong demonstration of clinical efficacy. Participants with signs and symptoms of CDI and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned to receive oral Ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. Participants receiving Ridinilazole were cured of the infection and remained disease-free for at least 30 days. In particular , Ridinilazole, gave a 50% increase in sustained clinical response compared to vancomycin, which is the current drug of choice for serious cases of C. difficile infection. Indeed, this meant that Ridinilazole demonstrated statistical superiority over standard-of-care vancomycin, which is a rare feat in antimicrobial trials. This demonstrates that the new insights into approaches for treating C. diff infections made possible by the underpinning work on BBZ compounds can lead to real clinical improvements [E4].

The success of the Phase 2 trial had a significant impact on the care of the patient group who received the drug and showed clinical benefit but moving forward this drug has the potential to dramatically improve the care of many thousands of patients annually.

The FDA has accorded the drug Fast Track (development) status and Qualified Infectious Disease Product status, which affords a number of advantages including an extension of marketing exclusivity for the drug [E5].

Phase 3 clinical trials, which began in Jan 2019, signal a major development in the treatment of an infection for which current therapies are ineffective and which causes tens of thousands of fatalities every year [E6], [E7]. It therefore has global reach and significance, as reflected in the level of investment for the Phase 3 clinical trial. Notably BARDA (Biomedical Advanced Research and Development Authority), an agency of the US government’s Department of Health and Human Services, has awarded Summit a contract worth up to USD62,000,000 to support the clinical and regulatory development of Ridinilazole [E8].

In Nov 2020, Summit announced the successful conclusion of a further USD50,000,000 investment round which will support commercial development of Ridinilazole [E9].