Patients frequently fall into a vicious cycle caused by Clostridium Difficile Market or C. diff. C. diff is a bacterial infection that typically affects people who have been treated with antibiotics and whose balance of gut bacteria has been disturbed. It causes persistent diarrhoea and GI symptoms.

Sadly, the infection can recur as treatment typically requires a second course of antibiotics.

The likelihood of recurrence increases with each subsequent episode, and approximately 20% of C. difficile patients will experience a second episode. A 40% chance of reinfection occurs in patients who have had two C. diff infections, rising to 60% after the third infection. Some recurrences are brought on by the initial infection returning, while others are brought on by being infected with a new strain.

According to Dr. James Tursi, chief scientific officer of Ferring Pharmaceuticals in the United States, "when you're treated for C. diff with antibiotics, what antibiotics will do is to disrupt your normal GI tract microbiome." That makes it possible for C. diff. that is already present to recur, whether it was acquired in a hospital or nursing home.

Although its efficacy in treating recurrent infections is unknown, the narrow-spectrum antibiotic fidaxomicin is currently used to treat C. difficile.

A faecal microbiota transplant can be extremely effective when drugs fail, and the monoclonal antibody bezlotoxumab is one of the available alternative treatments.

However, the infection continues to be burdensome for healthcare systems and incapacitating for patients. The overall mortality rate hovers around 2% and rises to 25% among the elderly and frail, with fatal outbreaks occurring annually in hospitals. Additionally, patients run the risk of fatal complications like sepsis.

RBX2660: a promising new strategy for C. difficile Ferring Pharmaceuticals, a Swiss pharmaceutical company, and its US subsidiary Rebiotix are employing a novel strategy for recurrent C. diff. In early-stage trials, their experimental compound, RBX2660, has demonstrated exceptional efficacy. It is a live biotherapeutic based on microbiota.

It works by bringing a wide variety of microbes into the gut, which makes the microbiome more diverse and lowers the risk of C. diff infection. The product can be standardized and the manufacturing process can be subjected to proper quality controls, in contrast to a faecal microbiota transplant, which is based on a similar principle. This treatment would be the first of its kind if it were approved.

According to Tursi, "our microbiome is a microbial community that is extremely diverse." We accept it's basic to human wellbeing, meaning it accomplishes something beyond exist. Dysbiosis, the disruption of that microbiome, can lead to issues.

There is a decrease in diversity and an increased likelihood of infection in a C. diff. patient. RBX2660's goal is to restore that diverse microbiome, thereby assisting the body in its own fight against C. diff.

Ferring and Rebiotix presented favorable results from their Phase III clinical trial, Punch CD3, during Digestive Disease Week in May. In patients with C. difficile recurrence, the biotherapeutic was found to be safe and effective for up to six months in their analysis.

70.4% of patients were free of C. diff eight weeks after receiving the treatment, compared to 58.1% in the placebo group. Most of the gastrointestinal side effects were mild or moderate, and they were comparable to those in the placebo group.

According to Tursi, "there was a clinically meaningful improvement." In terms of improvement, there was an absolute difference of 12.3% when compared to the placebo.

“Compared to the placebo, the relative reduction in C. diff infection recurrence was 29.4%, which was statistically significant. It was very exciting that we were able to demonstrate these statistically significant results.

Treating patients in a real-world setting The team also presented the findings of the related open-label PUNCH CD3 study, which revealed a pattern that was similarly encouraging. 75% of participants were free of C. diff infection eight weeks after the interim analysis. Seventy-four percent of those who completed the six-month follow-up (roughly half of the participants) remained symptom-free.

The fact that the open-label study included patients with co-morbid conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), which are typically excluded from C. difficile trials, made it interesting.

According to Tursi, "the open-label study was conducted primarily to expand the opportunity for patients to be treated in a setting that is more representative of the real world."

These are patients who typically present with C. diff in a doctor's office. These patients were excluded from the Phase III double-blind placebo-controlled program due to stricter inclusion criteria. However, they were included in the open-label to demonstrate their safety and efficacy.

Although they haven't specified when, Ferring and Rebiotix are eager to share their data with the FDA.

According to Tursi, "we believe that RBX2660 holds the potential to create an improvement over what is standard of care and, ideally, provide benefit for patients who are suffering from this severe disease." RBX2660 is a potential treatment option.

At the forefront of microbiome research Although the microbiome is a topic that has received a lot of attention, the search for therapies based on the microbiota is still in its infancy, and the anticipated wave of treatments that use the power of gut bacteria has not yet arrived.

According to Tursi, "This is a relatively new area, and when I was in clinical practice 20 years ago, it was never done." There was no conclusive placebo-controlled evidence to demonstrate that altering the microbiome can have an impact on disease.

"What RBX2660 offers is a product that has undergone stringent Phase III testing, we believe has demonstrated efficacy and tolerability, and offers the promise of a product that might be approved by the FDA to reduce recurrent C. diff. infections," the company states. If approved, it would be the first.

Additionally, Ferring and Rebiotix are investigating RBX7455, an oral version of RBX2660 that has successfully completed a Phase I study. The oral formulation was created with the intention of making repeat dosing simpler.

In order to find out what microbiome therapy might one day accomplish, they are also investigating other potential fields, not just the digestive system.

According to Tursi, "Ferring has what we believe to be the largest database for live biotherapeutics in the reduction of recurrent C. diff," "compulsive donor screening," and "a broad consortium of diverse microbes" are all crucial to success.

"Being involved in that potential first-in-class approval, that first product coming out, is the most exciting thing in the pharmaceutical industry. This is truly innovative.