A New Gold Standard for C. diff Therapy Could be in the Offing;
Next Data Release Expected in 2Q23
Clostridioides difficile/Clostridium difficile (C. diff) is a bacterial infection and is the most common cause of healthcare-associated diarrhea. C. diff has two distinct presentations, primary and recurrent infection. Primary C. diff is defined as the first episode of C. diff, while recurrent C. diff refers to the second or additional episodes following the primary infection. Re-infection occurs in up to 35% of individuals, with the risk of recurrence increasing with each episode.
“Recurrence is the key cause of C. diff mortality and the principal contributor of C. diff’s more than two billion dollars in annual cost to the U.S. healthcare system,” says David Luci, CEO of Acurx Pharmaceuticals (NASDAQ: ACXP), which is currently in Phase 2 clinical trials with a drug candidate that is showing high promise in curing C. diff infections in patients with primary C. diff or recurrent C. diff and, at the same time, preventing recurrence
In a Phase 2a study of the company’s C. diff candidate, called ibezapolstat, all ten patients enrolled were clinically cured of infection within two days of the end of treatment with no recurrence of C. diff at the 28-day follow-up visit. The positive clinical and safety results coupled with the beneficial effects on the gut microbiome resulted in the early termination of the study, and provided the first clinical hint of ibezapolstat’s potential superiority over vancomycin based on historical data.
A 64-patient Phase 2b study is currently enrolling patients to further assess the efficacy and safety of ibezapolstat and its effects on the gut microbiome compared to vancomycin. The study will evaluate the comparative effects of ibezapolstat on clinical cure and sustained clinical cure (defined as clinical cure at the end of treatment visit and no recurrence within 28 days).
It is expected that study enrollment will complete in 1Q 2023, with the release of interim results planned for 2Q 2023.
Costly, Age Indifferent Infection with High Death Rate
C. diff affects individuals of any age and is associated with significant and troublesome symptoms and mortality. Over the past decades, there has been a rapid increase in the incidence of community-acquired infection. C. diff has a profound economic impact on the healthcare system and patients due to recurrences, hospitalization, prolonged length of stay, and the cost of treatment which amount to roughly $2.8 billion dollars annually in the U.S—not to mention indirect societal costs such as loss of paid employment, and family disruptions.
Vacnomycin has been the gold-standard antibiotic for treating C. diff and many other life-threatening infections since its introduction in 1965.
“It’s a great drug. It has lasted roughly six decades as the go-to therapy for C. diff with very little competition”, notes Mr. Luci. “But its growing weakness, especially in preventing re-infection, has left a grizzly trail of serious sickness and a death rate of about 20,000 annually in the U.S. alone.”
Clinical data collected over the years indicates that a typical new antibiotic has a peak efficacy of about five years and thereafter the process of antimicrobial resistance begins to set in —”a process by which bacteria learn to identify an antibiotic as a medicine and then find a way to morph their properties to avoid being killed by it,” explains Mr. Luci. “That’s why most antibiotics become less and less effective over time.”
With today’s approved therapies, the estimated C. diff recurrence rate is around 20% after the initial treatment, increasing to 60% after multiple recurrences.
Ibezapolstat – Gentle on Gut Flora Whilst Targeting Drug-Resistant Disease-Causing Bacteria
The gut microbiome (also called gut flora) consists of trillions of microorganisms – such as bacteria and viruses – living inside the digestive tract. These microbes play an essential role in health, helping to break down food, absorb nutrients, and to protect against disease-causing microorganisms. Research has shown that changes in the composition and diversity of gut microbiomes can dramatically affect physical and mental well-being.
A recently published Phase 1 study of Ibezapolstat in 10 healthy volunteers demonstrated that that Acrux’s C. diff candidate was effective against C. diff and caused changes in the structure and behavior of disease-causing bacteria, but not healthy bacteria.
The results suggest that ibezapolstat is associated with a lower risk of C. diff recurrence than vancomycin.
Furthermore, ibezapolstat did not adversely affect the gut microbiome, whilst vancomycin had undesirable effects on the gut microbiome and was ineffectual against drug-resistant bacteria.
Current data would suggest that Ibezapolstat seems to be on a solid trajectory to become a first-line treatment for C. diff infection, given its ability to affect a total reduction in recurrence rates, would could lead to improvements in morbidity and mortality and a significant savings in healthcare and societal costs.
This is in stark contrast to the failure of Pfizer’s PFE vaccine candidate PF-06425090 and the antibiotics cadazolid (investigated by Johnson & Johnson JNJ) and surotomycin (investigated by Merck & Co MRK) to meet their primary outcomes. More recently, in September 2022, Summit Therapeutics SMMT decided to furlough development of ridinilazole for pediatric C. diff, and in January of this year, Finch Therapeutics Group FNCH ended its development work on a fecal transplant technology for recurrent C. diff.
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