お知らせ • Sep 12
Seres Therapeutics, Inc. Announces Topline Clinical Data from Cohort 2 of its SER-155 Phase 1b Placebo-Controlled Study in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Seres Therapeutics, Inc. announced on September 12, 2024, the company announced topline clinical data from Cohort 2 of its SER-155 Phase 1b placebo-controlled study in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Study results demonstrate that SER-155 was associated with a significant reduction in both bloodstream infections (BSIs) and systemic antibiotic exposure, as well as a lower incidence of febrile neutropenia, as compared to placebo through day 100 post HSCT. The Company believes that the SER-155 Phase 1 study results support the Company’s corporate strategy to develop its platform, comprised of a pipeline of designed live biotherapeutics, in multiple medically vulnerable patient populations at high risk of life-threatening bacterial infections and associated negative clinical outcomes. The Company intends to seek Breakthrough Therapy designation, given the high unmet medical need associated with BSIs, and discuss advancing development of SER-155 for allo-HSCT with the U.S. Food and Drug Administration (FDA). The Company also intends to evaluate SER-155 in additional patient populations that have a high risk of serious bacterial infections. SER-155 Phase 1b Study Design: The SER-155 Phase 1b study (NCT04995653) included two cohorts. Cohort 1 was designed to assess safety and drug pharmacology, specifically the drug strain engraftment in the gastrointestinal tract. Cohort 1 included 13 subjects who received any dosing of the SER-155 regimen, with 11 subjects subsequently receiving an allo-HSCT. Results from this cohort, announced in May 2023, showed SER-155 was generally well tolerated and resulted in successful drug strain engraftment and a reduction in pathogen domination in the GI microbiome relative to a historical control cohort. Study Cohort 2 utilized a randomized, double-blinded 1:1 placebo-controlled design to further evaluate safety and drug strain engraftment, as well as key secondary and exploratory endpoints such as the incidence of bacterial bloodstream infections and related medical consequences such as febrile neutropenia and antibiotic use. Cohort 2 included 45 patients in the intention-to-treat (ITT) population. Of the ITT population, 20 received SER-155 and 14 received placebo, each of whom subsequently received an allo-HSCT, with data available for clinical evaluation through day 100, the study’s prespecified primary observation point. Exploratory hypothesis testing was conducted at the two-sided a=0.05 level. 95% 2-sided confidence intervals (CIs) were determined, where specified. No adjustment for multiplicity was done. A subset of patient samples was available for drug pharmacology analysis. The median age in Cohort 2 was 63, and most subjects had acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome or myeloproliferative neoplasia as their primary disease and received reduced-intensity conditioning pre-transplant. Most patients received peripheral blood stem cells from a matched unrelated donor. A majority received post-transplant cyclophosphamide as part of their graft-versus-host disease (GvHD) prophylaxis. Summary of Cohort 2 Study Results: Consistent with the observations from the Phase 1b study Cohort 1, SER-155 was generally well-tolerated, and no treatment-emergent serious adverse events related to drug were observed. SER-155 bacterial strains engrafted into the gastrointestinal tract of patients following the administration of SER-155. The incidence of BSIs was significantly lower in the SER-155 arm compared with the placebo arm (2/20 (10%) vs. 6/14 (42.9%), respectively; [Odds Ratio: 0.15; 95% CI: 0.01, 1.13, p=0.0423]). In addition, while antibiotic starts were similar in each arm, patients administered SER-155 were treated with antibiotics for a significantly shorter duration compared to patients in the placebo arm (9.2 days vs. 21.1 days, respectively, with a mean difference of -11.9 days [95% CI: -23.85, -0.04; p=0.0494]). The incidence of febrile neutropenia was lower in patients administered SER-155 compared to placebo (65% vs. 78.6%, respectively; [Odds Ratio: 0.51; 95% CI: 0.07, 2.99; p=0.4674]). Six cases of gastrointestinal infections (C. difficile infections) were observed in the study, with four cases (20%) in the SER-155 arm and two cases (14.3%) in the placebo arm. Recent changes in the allo-HSCT standard of care and the increasing use of post-transplant cyclophosphamide as part of prophylactic therapy for GvHD have reduced rates of GvHD overall in this patient population. The rates of GvHD in the study were low, with two cases of grade 2 GvHD observed in each arm, and no cases of grade 3 or 4 GvHD were observed. In Cohort 2, the ability to detect pathogen domination (i.e., relative abundance in the GI =30%) in the placebo arm, and differences between the study arms, was constrained due to the limited number of placebo stool samples and an imbalance in the number of available stool samples between the arms. Observed pathogen domination events were low in the placebo and SER-155 arms with no significant differences identified. In a comparison of the prevalence of pathogen domination versus a larger allo-HSCT historical control cohort, pathogen domination in SER-155 subjects was substantially lower, providing further evidence of SER-155 activity. The overall safety results in the first 100 days showed that SER-155 was generally well-tolerated, with no observed treatment-related serious adverse events. In Cohort 2, all but one subject in the placebo arm experienced at least one treatment-emergent adverse event (“TEAE”). The most common TEAEs were diarrhea and nausea. Four subjects experienced TEAEs that led to discontinuation. Nineteen subjects, or 48% of subjects, experienced serious adverse events, none of which were considered related to SER-155. Three deaths were reported in the study, none of which were considered related to SER-155. Fourteen subjects, or 35% of the subjects, experienced adverse events of special interest, including bloodstream infections, GI infection and invasive infection. Seres fully owns worldwide rights for the commercialization of SER-155.