Oral SER-109 Effectively Prevents C Difficile Recurrences in Open-Label Study

Oral treatment with SER-109 following antibiotic therapy effectively prevented clostridioides difficile infection (CDI) recurrences for most patients receiving the microbiome therapeutic, according to findings from the open-label phase 3 ECOSPOR IV trial presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.

Across all patients in the single-arm study (n = 263), the recurrence rate was 8.7% at week 8, which remained consistent across subgroups. In those with 1 recurrence of CDI at baseline, the recurrence rate was 6.5% with SER-109 and for those with 2 or more recurrences the rate was 9.7%. Treatment-emergent adverse events (TEAEs) were seen in 52% of patients, with 32 TEAEs related or possibly related to treatment.

"Rate of recurrent CDI were low through week 8, regardless of the number of prior episodes, supporting the potential benefit of SER-109 following antibiotics for recurrent CDI," lead author Sahil Khanna, MBBS, MS, FACG, Mayo Clinic, Rochester, MN, said during a presentation of the results. "Earlier intervention with SER-109 in first recurrence may reduce the healthcare burden of further CDI episodes."

SER-109 is manufactured through an inactivation of donor vegetative bacteria, parasites, fungi, and viruses using ethanol. After this process, the remaining product contains purified firmicutes spores, which are resistant to gastric acid and allows for oral administration. SER-109 is given in 4 capsules on days 1 to 3, after which the spores germinate and replicate in the GI tract.

In the prior ECOSPOR III study, which was published in the New England Journal of Medicine, SER-109 was superior to placebo in reducing the risk of Recurrent CDI. In this trial, at 8 weeks, there was sustained clinical remission for 88% of those treated with SER-109 compared with 60% for those in the placebo group. The relative risk of recurrence was 40% with placebo compared with 12% with SER-109, representing a 28 percentage point difference. Most recurrences happened early, with few after week 8, Khanna noted.

Based on the collection of findings with SER-109, the FDA has accepted a biologics license application for the agent to prevent recurrent CDI. The agency set a Prescription Drug User Fee Act (PDUFA) data of April 26, 2023.

The ECOSPOR IV study included 29 patients from the ECOSPOR III study with recurrent CDI. These patients were mostly enrolled to the placebo arm (n = 25), with 4 from the SER-109 group who received retreatment with the therapy. The remaining 234 patients were de novo subjects with 1 or more CDI recurrences. All patients were on 10 oz mg citrate 1 day prior to dosing, given the ethanol used to purify the treatment, Khanna said.

The mean age of all patients in the study (N = 263) was 64.0 years, with 52% over the age of 65. Two-thirds of patients were female (68%) and most had 2 or more CDI recurrences (71%). The most common prior antibiotic was vancomycin (73%) and CDI was defined as toxin with or without PCR for 74% of patients. The most common comorbidities at baseline included cardiac disorders and neoplasms, with a mean Charlson comorbidity index score of 3.8.

By prior antibiotic, the recurrence rate was 8.9% for those receiving prior vancomycin prior to SER-109 administration. In those receiving prior fidaxomicin, the recurrence rate was 8.3% with SER-109.

Across all patients, 12% experienced a related or possibly related TEAE to SER-109. TEAEs across the full group, regardless of cause, were mild to moderate for 45% of patients. Serious TEAEs were experienced by 8% of patients, with none related or possibly related to the study drug. There were 8 deaths from TEAEs through week 24, but none were deemed related to SER-109.

"SER-109 was well-tolerated in this patient population with multiple comorbidities," said Khanna. "These data extend the findings of ECOSPOR III in an expanded patient population."

The oral abstract, “An Open-Label Study (ECOSPOR IV) to Evaluate the Safety, Efficacy and Durability of SER-109 in Adults with Recurrent Clostridioides difficile Infection (rCDI),” was presented at ACG 2022.