Seres' SER-155 bacterial capsule linked to fewer bloodstream infections in phase 1b transplant trial
In a phase 1b trial in allogeneic stem cell transplant recipients, oral SER-155 had a safety profile like placebo and was linked to fewer bloodstream infections.
Nature Medicine has published results of a phase 1b study of SER-155, an investigational oral live biotherapeutic made of cultivated bacterial strains. The study enrolled recipients of allogeneic hematopoietic cell transplant in two cohorts: an open-label cohort of 15 participants and a randomized, placebo-controlled cohort of 45. nature.com
Nature Medicinenature.comOpen source ↗ The product is meant to address disruption of the gastrointestinal microbiome and of the intestinal epithelial barrier, which raise the risk of bloodstream infection after transplant.
In the randomized cohort, 34 of 45 participants received treatment or placebo and then underwent transplant. Twenty received SER-155 after microbiome conditioning with oral vancomycin, and 14 received placebo.
Safety and engraftment
The primary endpoint was safety. According to the authors, SER-155 was well tolerated, with a profile comparable to placebo, no treatment-related serious adverse events and no infections with SER-155 species. The most common adverse events were diarrhea and nausea. Four participants in cohort 1 and four in cohort 2 died during the study, two of them in the SER-155 arm and two in the placebo arm. None of the deaths was attributed to SER-155.
The primary pharmacokinetic endpoint was engraftment of the administered bacteria. All 16 SER-155 strains were detected, with a median of 11.5 strains found after the first treatment course. nature.com
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Infection outcomes
The key secondary efficacy endpoint was the incidence of bloodstream infection. It was 10.0% with SER-155 and 43% with placebo (odds ratio 0.15; 95% CI 0.01–1.13; P = 0.0423), a 77% relative risk reduction.
The other secondary efficacy endpoints did not reach statistical significance: gastrointestinal infection, acute graft-versus-host disease of grade 2 or higher, febrile neutropenia, and a composite of bloodstream infection, gastrointestinal infection or acute graft-versus-host disease. The secondary pharmacodynamic endpoint, gastrointestinal domination by Enterococcus and Enterobacteriaceae species, was not achieved.
The randomized cohort was small, and the confidence interval for the odds ratio is wide. The authors conclude that the results warrant further clinical investigation of SER-155. The study is registered on ClinicalTrials.gov as NCT04995653. nature.com
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