SER-109 Reduces Volume of Recurrent C Difficile Infection in Immunocompromised Patients

SER-109 was superior to placebo in reducing the volume of Clostridium difficile infection (CDI) as early as 4 weeks posttreatment, according to findings from phase 3 ECOSPORIII trial (NCT03183128). The data, which were presented in a poster at the 2022 ASCO Annual Meeting, highlighted the possible clinical benefit of early microbiome repair in patients experiencing recurrent CDI.

At 4 weeks posttreatment, the cumulative rate of recurrent CDI was 11.2% in the SER-109 arm (n = 89) vs 33.3% in the placebo arm (n = 93; relative risk [RR], 0.35; 95% CI, 0.19-0.67). At 12 weeks posttreatment, the rates were 18.0% vs 46.2%, respectively (RR, 0.40, 95% CI, 0.24-0.73).

At 24 weeks posttreatment, the cumulative rate of recurrent CDI was 21.3% in the investigational arm vs 47.3% in the placebo (RR, 0.46, 95% CI, 0.30-0.73), demonstrating the sustained benefit of SER-109.

Previous reports found that that SER-109 was superior to placebo in reducing CDI rates at 8 weeks—meeting the trial’s primary end point. The rate of recurrence in the intention-to-treat population was 12.4% with SER-109 vs 39.8% with placebo (RR 0.32, 95% CI, 0.18-0.58; P < .001) with 11 incidences of recurrence among the 89 subjects assigned to SER-109 and 37 events among the 93 patients receiving placebo.

“[CDI] is associated with high mortality and patients with malignancy and immunosuppression are at an increased risk for CDI and worse outcomes due to their immunosuppression state and exposure to antibiotics and chemotherapy, which facilitate C difficile colonization, outgrowth, and toxin production through microbiome disruption,” the study authors wrote in the poster.

SER-109 is an investigational, oral microbiome therapy made up of live, purified Firmucyes bacterial spores, designed to lower the risk of CDI recurrence.

ECOSPORIII was a phase 3, double blind, placebo-controlled trial which enrolled 281 adult patients with recurrent CDI to receive either 4 oral capsules of SER-109 once daily for 3 days or placebo. The study defined CDI as 3 or greater unformed stools per day for at least 48 hours with a positive C difficile toxin assay. Recurrence was determined by 3 components including 3 or more unformed stools per day over 2 consecutive days with persistent diarrhea until antibiotic treatment, a positive C difficile assay, and investigator assessment confirming antibiotic treatment was warranted.

Eligible participants had at least 3 episodes of CDI within 12 months and were screened across 56 sites in the US and Canada. A total of 182 individuals who experienced symptom resolution on antibiotics for 10 to 21 days and received 10 oz magnesium citrate to minimize residual antibiotics were randomly assigned to SER-109 or placebo. All subjects had acute infection and chronic suppressive antibiotics were permitted.

Subjects were stratified by age (≥ 65 years vs < 65 years) and antibiotics received (fidaxomicin vs vancomycin).

At baseline, 36.3% of patients had respiratory disease, 32.5% had cardiovascular disease, and 28.6% of patients had immunocompromised status, which are historically associated with risk of recurrence. In addition, 23.6% had diabetes, 12.6% had a renal impairment or failure, and 12.6% had a neurologic disease. Thirty-three patients were identified as having a malignancy at baseline, the definition of which included several tumor types such as breast cancer, chronic lymphocytic leukemia, colon cancer, endometrial cancer, malignant melanoma, prostate cancer, and others.

Further, 73% of patients had a Charlson Comorbidity Index score greater than of 3 or greater; 38% of patients (n = 70) had a score of 5 or greater, 35% of patients (n = 63) had a score between 3 to 4, 18% (n = 32) of had a score of 1 to 2, and 9% (n = 17) of patients had a score of 0.

In the safety population, patients treated with SER-109 (n = 90) had comparable rates of treatment-emergent adverse events (TRAEs) vs placebo (n = 92). An analysis of TRAEs occurring in 5% or more of patients through week 24 showed that flatulence was the most common event, occurring in 70% of patients receiving SER-109 and 76.1% of patients receiving placebo. Other common TRAEs included fatigue (58.9% vs 63.0%, respectively), abdominal distention (54.4% vs 53.3%), abdominal pain (51.1% vs 60.9%), constipation (31.1% vs 23.9%), decreased appetite (28.9% vs 37.0%), diarrhea (24.4% vs 21.7%), and chills (23.3% vs 23.9%).

Nausea, urinary tract infection, vomiting, and Clostridioides difficile colitis also occurred–although these TREAs were less frequent. In the SER-109 vs placebo arms, 17.8% vs 32.6% of patients experienced nausea, respectively; 8.9% vs 1.1% experienced a urinary tract infection; 3.3% vs 10.9% experienced vomiting; and 1.1 vs 8.7% experienced colitis.

“SER-109 may represent a potential paradigm shift in the clinical management of patients with recurrent CDI, including those with malignancies and immunocompromised status,” study authors concluded.

Reference

Paskovaty A, Berenson CS, Louie TJ, Louice TJ, Lombardi DA, von Moltke L. Efficacy and safety of SER-109, an investigational microbiome therapeutic for recurrent clostridioiodes difficile infection: data from ECOSPOR III, a phase 3 randomized trial. J Clin Oncol. 2022;40(suppl 16):12113. doi:10.1200/JCO.2022.40.16_suppl.12113