Promising Outcomes for SER-109: A New Approach to Managing Recurrent CDI

Clostridioides difficile infection (CDI) is common in vulnerable patient populations. Vulnerable populations include:¹

• Adult individuals;
• Individuals with compromised immunes systems; and
• Individuals with underlying medical conditions (eg, cancer, chronic kidney disease, and other comorbidities).

It can also be considered as a hospital-acquired infection.² The primary risk factor for CDI is prior exposure to broad-spectrum antibiotics, which disrupt the gastrointestinal microbiome. This crucial ecosystem serves as the body's primary defense against potential pathogens like C difficile. However, C difficile spores can survive in an environment for extended periods of time, and are resistant to most disinfectants and cleaning agents.²

Hospitals and health care facilities aim to prevent the spread to the best of their ability, but the associated costs make it difficult. Hospitals implement strategies to combat this barrier by establishing visitor contact precautions, patient hand hygiene, and health care worker hand hygiene alone.³

Researchers analyzed 13 studies to assess hospital-onset CDI in the past, and found that the CDI incidence rate was 8.3 cases per 10,000 patient days. In 16 out of 20 studies that used propensity score matching, the difference in length of hospital stay between patients with CDI and those without CDI varied from 3 days (95% CI, 1.44-4.63) to as much as 21.6 days (95% CI, 19.29-23.90).⁴ To fully understand how to diminish hospital length of stays and overall recurrence, researchers explored treatment options to mitigate that.

According to a study published in JAMA Network Open, health care professionals also see an uptick CDI in younger individuals despite lacking traditional risk factors. CDI results in a significant health care burden, leading to higher hospitalization and mortality rates among inpatients diagnosed with CDI.¹ It is unclear whether or not this results from hospital exposure, patient hygiene, or health care worker hygiene.

CDI's tendency to recur despite appropriate antibiotic treatment and safety precautions highlights the limitations of current therapeutic approaches. Antibiotics like vancomycin and fidaxomicin, effective against C difficile bacteria, can resolve diarrhea in days. However, although both effectively kill the C difficile bacteria in its vegetative form, researchers found they do not restore the microbiome they disrupt during treatment. Because of this, many patients experience recurrence due to the persistence of C difficile spores and alterations in the gut flora. Patients with recurrent CDI are at a higher risk of subsequent episodes, with recurrence rates often exceeding 40%.¹

SER-109, an investigational oral microbiome therapeutic composed of purified Firmicutes spores, demonstrated superiority over a placebo in reducing the risk of recurrent CDI in patients with multiple CDI recurrences. This trial, known as ECOSPOR IV, aimed to expand on these findings and provide insights into SER-109's efficacy and safety in a broader patient population with a history of CDI.¹

ECOSPOR IV was a phase-3, open-label, single-arm trial conducted at multiple sites in the US and Canada from October 2017 to April 2022. The trial was designed to meet the US Food and Drug Administration's safety database requirements, and it followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.¹

The study included two cohorts of adults aged 18 years and older. Cohort 1 consisted of patients from the ECOSPOR III trial who had experienced a CDI recurrence within 8 weeks after receiving either SER-109 or a placebo. Cohort 2 included new patients with at least one CDI recurrence. According to researchers, specific clinical criteria, including the number of unformed stools per day, positive test results for C difficile toxins, and a response to CDI antibiotic treatment, defined the recurrence of CDI. The study lasted approximately 27 weeks, with a 3-week screening period, an 8-week primary efficacy period, and a 16-week follow-up period.¹

All patients received SER-109 as a daily dose, with specific dosing instructions to ensure the effectiveness of the treatment. Comorbidities were common in the patient population, with a high mean Charlson Comorbidity Index score indicating an increased mortality risk. The trial's safety data showed that SER-109 was well-tolerated, with most adverse events being mild to moderate and unrelated to the treatment. There were no deaths or serious adverse events attributed to SER-109.¹

The trial's primary endpoint was to evaluate the safety and tolerability of SER-109 over 24 weeks. In contrast, the secondary endpoint was CDI recurrence rates at weeks 4, 8, 12, and 24 after the initiation of treatment. The trial data showed low CDI recurrence rates, with sustained clinical response rates of over 90% at 8 weeks and over 86% at 24 weeks. The low recurrence rates were consistent across different subgroups, including patients with different ages, antibiotic regimens, and diagnostic methods.¹

Results of the ECOSPOR IV trial indicate that SER-109 was well-tolerated and associated with low rates of CDI recurrence in a patient population at high risk of recurrent disease. These findings support the potential role of SER-109 as part of a new approach to managing recurrent CDI, especially if administered at the time of the first recurrence, which may reduce morbidity and health care costs associated with recurrent CDI.¹

"These data support an important role for SER-109 as part of a paradigm shift in the clinical management of recurrent CDI," said researchers. Not only does SER-109 effectively treat CDI, but results show that it can even reduce recurrence. A major benefit when it comes to associated health care costs for patients.

Reference

1. Sims MD, Khanna S, Feuerstadt P, et al. Safety and tolerability of SER-109 as an investigational microbiome therapeutic in adults with recurrent Clostridioides difficile infection: A phase 3, open-label, single-arm trial. JAMA Network Open. 2023;6(2):e2255758. doi:10.1001/jamanetworkopen.2022.55758
2. Miller A, Segre AM, Pemmaraju SV, Sewell DK, Polgreen PM. Association of Household exposure to primary Clostridioides difficile infection with secondary infection in family members. JAMA Network Open. 2020;3(6):e208925-e208925. doi:10.1001/jamanetworkopen.2020.8925
3. Barker AK, Scaria E, Safdar N, Alagoz O. Evaluation of the cost-effectiveness of infection control strategies to reduce hospital-onset Clostridioides difficile infection. JAMA Network Open. 2020;3(8):e2012522. doi:10.1001/jamanetworkopen.2020.12522
4. Marra AR, Perencevich EN, Nelson RE, et al. Incidence and outcomes associated with Clostridium difficile infections. JAMA Network Open. 2020;3(1):e1917597. doi:10.1001/jamanetworkopen.2019.17597