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Review
. 2022 Sep 10;11(9):1234.
doi: 10.3390/antibiotics11091234.

SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)

Sahil Khanna  1 , Matthew Sims  2   3 , Thomas J Louie  4 , Monika Fischer  5 , Kerry LaPlante  6   7 , Jessica Allegretti  8 , Brooke R Hasson  9 , Allyson T Fonte  9 , Christopher McChalicher  9 , David S Ege  9 , Jessica A Bryant  9 , Timothy J Straub  9 , Christopher B Ford  9 , Matthew R Henn  9 , Elaine E L Wang  9 , Lisa von Moltke  9 , Mark H Wilcox  10
Affiliations
Review

SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)

Sahil Khanna et al. Antibiotics (Basel). .

Abstract

Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20−25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p < 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response.

Keywords: Clostridioides difficile infection (CDI); Firmicutes; SER-109; microbial diversity; microbiome therapeutics; recurrent CDI.

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Conflict of interest statement

S.K. receives research support from Rebioitx/Ferring, Vedanta, Finch, Seres Therapeutics, and Pfizer, and serves as a consultant for Probio Tech, LLC; Shire/Takeda, Niche and Immuron. M.F. served on the Data Saftey Monitoring Board for Rebiotix, and is a consultant for Scioto and an unpaid consultant for Openbiome. J.A. serves as a consultant for Finch Therapeutics, Seres Therapeutics, Ferring, Pfizer, Janssen, Bristol Myers Squibb, Artugen, Iterative Scopes, Abbvie, and Merck, had research support from Pfizer, Janssen, and Merck, and serves on the speaker bureau for Bristol Myers Squibb and Abbvie. K.L. has received research funding from Merck, is an advisor to Seres Therapeutics, and serves on the Advisory Board for Ferring Pharmaceuticals. M.S. serves as an advisory board member for Prenosis and as a principal investigator or coinvestigator for the following companies: Astra Zeneca, ContraFect, Crestone, Curetis GmBH, DiaSorin Molecular LLC, Epigenomics Inc., EUROIMMUN US, Finch Therapeutics, Genentech USA Inc., Janssen Research and Development, LLC, Kinevant Sciences GmBH, Leonard-Meron Biosciences, Lysovant, Merck, Prenosis, QIAGEN Sciences, LC, Regeneron Pharmaceuticals, Roche, Seres Therapeutics, Shire, and Summit Therapeutics. T.J.L. reports receiving grants and personal fees from Seres Therapeutics, Finch Therapeutics, Artugen, Summit PLC, Ferring, Vedanta Biosciences, and Crestone. M.H.W. has received consulting fees from AiCuris, Bayer, Crestone, Da Volterra, Dinove, EnteroBiotix, The European Tissue Symposium, Ferring, GSK, Menarini, Merck, Nestlé, Paion, Paratek, Pfizer, Phico Therapeutics, Qpex Biopharma, Seres Therapeutics, Surface Skins, Summit, Tillotts, Vaxxilon/Idorsia and Vedanta; lecture fees from GSK, Merck, Pfizer, and Seres Therapeutics; and grant support from Almirall, Da Volterra, EnteroBiotix, GSK, Merck, MicroPharm, Nabriva, Paratex, Pfizer, Seres Therapeutics, Summit, The European Tissue Symposium and Tillotts. C.M., D.S.E., C.B.F., J.A.B., T.J.S., B.R.H., A.T.F., L.M., E.E.L.W., and M.R.H. are all employees and shareholders of Seres Therapeutics.

Figures

Figure 1
Figure 1
C. difficile infection (CDI) is a two-hit process requiring a 2-pronged treatment approach.
Figure 2
Figure 2
SER-109 Manufacturing processes mitigate risk.
Figure 3
Figure 3
SER-109 engraftment and metabolomics.
See this image and copyright information in PMC

References

    1. CDC . Antibiotic Resistance Threats in the United States. Department of Health and Human Services, CDC; Atlanta, GA, USA: 2019. [(accessed on 27 July 2022)]. Available online: www.cdc.gov/DrugResistance/Biggest-Threats.html.
    1. Magill S.S., Edwards J.R., Bamberg W., Beldavs Z.G., Dumyati G., Kainer M.A., Lynfield R., Maloney M., McAllister-Hollod L., Nadle J., et al. Multistate Point-Prevalence Survey of Health Care—Associated Infections. N. Engl. J. Med. 2014;370:1198–1208. doi: 10.1056/NEJMoa1306801. - DOI - PMC - PubMed
    1. Kwon J.H., Olsen M.A., Dubberke E.R. The Morbidity, Mortality, and Costs Associated with Clostridium Difficile Infection. Infect. Dis. Clin. 2015;29:123–134. doi: 10.1016/j.idc.2014.11.003. - DOI - PubMed
    1. UK Health Security Agency . Thirty-Day All-Cause Mortality Following MRSA, MSSA and Gram-Negative Bacteraemia and C. Difficile Infections, 2020 to 2021. UK Health Security Agency; London, UK: 2021.
    1. Guh A.Y., Mu Y., Winston L.G., Johnston H., Olson D., Farley M.M., Wilson L.E., Holzbauer S.M., Phipps E.C., Dumyati G.K., et al. Trends in U.S. Burden of Clostridioides Difficile Infection and Outcomes. N. Engl. J. Med. 2020;382:1320–1330. doi: 10.1056/NEJMoa1910215. - DOI - PMC - PubMed

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