麻豆传媒

WASHINGTON -- Extended follow-up of a phase III trial demonstrated continued benefit for an investigational microbiome therapeutic for patients with recurrent Clostridioides difficile infections.

Of the 182 patients in the randomized trial, C. difficile recurrence at 24 weeks occurred in 21.3% of patients who were treated with the oral therapy, SER-109, versus 47.3% of those given placebo (RR 0.46, 95% CI 0.30-0.73, P<0.001), reported Barbara McGovern, MD, of developer Seres in Cambridge, Massachusetts.

"Patients with recurrent C. difficile have a decimated microbiome, usually from multiple exposures to antibiotics," said McGovern at the annual meeting here.

The updated analysis, which was published simultaneously in , builds on previously reported 8-week findings -- the multicenter study's primary endpoint -- which showed a significantly lower recurrence rate with the microbiome therapy versus placebo (12% vs 40%, respectively) for patients who had been treated with standard antibiotics for three or more episodes of C. difficile infection.

SER-109's benefit was evident as early as week 2, according to the new findings, with significantly lower rates of recurrence also seen at weeks 4 and 12.

The sustained responses may be due to changes that the drug initiates in the patient microbiome, McGovern explained. "Microbiome data suggest that these clinical outcomes are due to changes in the microbiome structure and function."

SER-109 is a consortium of highly purified Firmicutes spores that "normally live in a healthy microbiome," said McGovern. "You may ask, why enrich for spore-forming Firmicutes? Well, they have a key role in preventing C. difficile spore germination and growth."

The spores are also resistant to gastric acid, she added, "allowing it to be put into oral capsules so the spores can germinate and replicate into the GI tract." Moreover, she said, the manufacturing processes inactivate vegetative bacteria, fungi, parasites, and viruses.

Patients in the study were randomized to receive SER-109 (n=89) or placebo (n=93) capsules four times a day for 3 days. Mean patient age was 65.5 years, and 59.9% were women. Most of the patients were white (93%), and 99% were outpatients.

Patients in both arms of the study had comorbidities, with a mean Charlson Comorbidity Index score of 4.1 in the SER-109 group and 4.2 in the placebo group. The most common treatment-related adverse events were flatulence, abdominal distention, abdominal pain, fatigue, and constipation. There were three deaths in the treatment group, and none in the placebo group; McGovern said the deaths were reported by a blinded investigator as unrelated to treatment.

Researchers counted patients who left the study early, were lost to follow-up, or died as recurrences. Patients who were missing components for recurrent C. difficile infection criteria (for example, having a positive toxin test result) were also counted as reinfected.

Limitations included that the study excluded patients in first recurrence, a subgroup with similar microbiome disruption.

In her presentation, McGovern also included limited data on a subsequent single-arm open-label study () that enrolled 263 patients. The trial was conducted to provide sufficient safety data to the FDA following a breakthrough therapy and orphan drug designation, and included patients with one or more episodes of C. difficile.

Seres last month that it is seeking approval for SER-109 in recurrent C. difficile.