Manufacturing Process of SER-109, a Purified Investigational Microbiome Therapeutic, Reduces Risk of Coronavirus Transmission From Donor Stool

Abstract

SARS-CoV-2 may present risk to patients treated with donor-derived microbiome therapies when lacking appropriate manufacturing controls and inactivation processes. We report that the manufacturing steps for SER-109, a purified investigational microbiome therapeutic developed to reduce risk of Clostridioides difficile recurrence, inactivate Porcine Epidemic Diarrhea Virus, a model coronavirus for SARS-CoV-2.

Efficacy and Practical Implementation of Fecal Microbiota Spores, Live-BRPK: A Novel Approach for Preventing Recurrent Clostridioides difficile Infection

“…VOS is isolated from human stool, collected from prescreened donors, purified through ethanol solvent and sequential purification and bioburden testing (Figure 1) (11). This process removes vegetative forms of bacteria, fungi, parasites, and viruses.…”

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection

“…24 The SER-109 manufacturing process delivers a purified consortium of Firmicutes spores, which play a key role in inhibiting C difficile while mitigating risk of transmitting undetected or emerging pathogens through inactivation of potential pathogens in donor product. 27,28 These defining features distinguish this purified consortium from fecal microbiota transplantation (FMT) and FMT-like products, which would be subject to transmission of undetected and emerging pathogens. 29 The recurrence rate in the overall study population was 8.7%, corresponding to a sustained clinical response rate at 8 weeks of 91.3%, which was durable over 24 weeks.…”

“…The mean Charlson Comorbidity Index score in the overall population was 3.8, indicative of high mortality risk . The SER-109 manufacturing process delivers a purified consortium of Firmicutes spores, which play a key role in inhibiting C difficile while mitigating risk of transmitting undetected or emerging pathogens through inactivation of potential pathogens in donor product . These defining features distinguish this purified consortium from fecal microbiota transplantation (FMT) and FMT-like products, which would be subject to transmission of undetected and emerging pathogens …”

“…The efficacy and safety data from the ECOSPOR III and ECOSPOR IV trials reinforce advantages of using a microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent CDI. The use of Firmicutes spores (1) achieves efficient drug delivery within the acidic environment of the stomach; (2) enables a low pill burden because spores can germinate, multiply, and replicate into metabolically active bacteria within the gastrointestinal tract; and (3) allows for specific inactivation of nonspore microorganisms during manufacturing, mitigating risks to patients . Spore-forming Firmicutes are thought to restore epithelial barrier integrity, decrease colonic inflammation, and modulate bile acid concentrations important to colonization resistance …”

Clostridioides difficile infection: microbe-microbe interactions and live biotherapeutics

“…SER-109 is another donor-derived therapeutic. The manufacturing of SER109 enriches Firmicute spores while inactivating potential bacterial, viral, and fungal pathogens ( McGovern et al, 2021 ; Feuerstadt et al, 2022 ; McChalicher et al, 2022 ). In a phase III clinical trial ( ClinicalTrials.gov Identifier: NCT03183128), subjects dosed with SER-109 were less likely to have recurrent infections following standard-of-care antibiotic treatment than patients in the placebo group ( Feuerstadt et al, 2022 ).…”