Investigators at IDWeek 2019 presented the final, 24-month analysis of data from a phase 2 open-label trial of RBX2660 for the prevention of CDI recurrence. Patients with multi-recurrent CDI were enrolled in the multicenter study and received > 2 doses of RBX2660 delivered via enema 7 days apart.
The research team defined efficacy as absence of CDI recurrence through 56 days after the last dose, and durability as continued absence of CDI episodes beyond 8 weeks. Results were compared with the 8-week recurrence-free rates for a historical control cohort that received standard-of-care antibiotic therapy.
Participant stool samples were collected prior to and for up to 720 days after treatment, and safety and durability assessments were performed at 3, 6 ,12, and 24 months. Investigators assessed microbiome changes via shallow shotgun sequencing.
Rebiotix Announces Expansion of Phase 1 Trial of the Company’s Oral Capsule Microbiota Product, RBX7455, Following Successful Completion of Initial Study Arms
Additional cohorts to examine potential of reduced dosing regimens of RBX7455 for the prevention of recurrent Clostridium difficile infection
Rebiotix Inc., a clinical-stage microbiome company
focused on harnessing the power of the human microbiome to treat challenging diseases, announced on November 30, 2017
an expansion of the investigator sponsored Phase 1 study of RBX7455 for the prevention of recurrent Clostridium difficile (C. diff.) infection. The expansion follows the successful completion of the study’s two initial cohorts and is intended to explore reduced dosing regimens of RBX7455 in two new treatment arms. RBX7455 is a lyophilized, non-frozen oral capsule formulation of Rebiotix’s Microbiota Restoration Therapy (MRT), a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad spectrum of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format.
“Expansion of the Phase 1 study is a key advancement in the development of RBX7455 as it provides an opportunity to explore the potential efficacy of reduced dosing regimens of our oral capsule product in the prevention of recurrent C. diff. infection,” stated Lee Jones, president and CEO of Rebiotix. “RBX7455 is a ground-breaking product in that its oral capsule design is the first in the microbiome industry not requiring storage in frozen conditions. As such, patients are able to administer RBX7455 at home as they would a typical oral capsule medication, which potentially makes RBX7455 ideally suited for diseases where chronic or repeat dosing is required.”
The Phase 1 study of RBX7455 is an investigator sponsored, prospective, single center, proof of concept dosing study of RBX7455 for the prevention of recurrent C. diff. infection. The first two arms enrolled 10 patients per arm (20 total). The expansion of the Phase 1 study adds two additional arms, which will enroll approximately 10 patients per arm (20 total) with reduced dosing regimens from the 2
first two arms. Rebiotix expects data from the first two cohorts of the Phase 1 study of RBX7455 to be released publicly by mid-2018.
In addition to the expanded Phase 1 study of RBX7455, Rebiotix’s clinical development pipeline is highlighted by the company’s ongoing Phase 3 clinical trial of RBX2660 for the prevention of recurrent C. diff. infection. RBX2660 is the first and only microbiome drug to be tested in three separate Phase 2 trials, with more than 300 subjects having been treated with the microbial therapy.
Recently, Rebiotix announced the presentation of research from the RBX2660 Phase 2 program demonstrating measurable evidence of the drug’s rehabilitative effect on the human microbiome and the potential advantages of its broad consortia design.
Ms. Jones continued, “We look forward to the continued progress of the RBX7455 Phase 1 study as well as our Phase 3 study of RBX2660, our lead microbiome drug candidate. Importantly, since both drugs were developed with our MRT platform, we can leverage knowledge from the extensive RBX2660 clinical program, as well as research into the drug’s rehabilitative impact on the gut microbiome, to inform and expedite the development of RBX7455.”
About Rebiotix Inc.
Rebiotix Inc. is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of challenging diseases. Rebiotix possesses a deep and diverse clinical pipeline, with its lead drug candidate, RBX2660, in Phase 3 clinical development for the prevention of recurrent Clostridium difficile (C. diff.) infection. RBX2660 has been granted Fast Track status, Orphan Drug and Breakthrough Therapy designation from the FDA for its potential to prevent recurrent C. diff. infection.
Rebiotix’s clinical pipeline also features RBX7455, a lyophilized nonfrozen,
oral capsule formulation, which is currently the subject of an investigator-sponsored Phase 1 trial for the prevention of recurrent C. diff. infection. In addition, Rebiotix is targeting several other disease states with drug products built on its pioneering Microbiota Restoration TherapyTM (MRT) platform.
MRT is a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract via a ready – to-use and easy-to-administer format. For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit www.rebiotix.com
Positive Topline Data from Open-Label Phase 2 Trial of RBX2660 in Recurrent Clostridium
difficile to be Presented for First Time
Rebiotix Inc., a clinical-stage microbiome company focused
on harnessing the power of the human microbiome to treat challenging diseases, today announced that three posters highlighting RBX2660 clinical and microbiome data will be featured at ID Week 2017 in San Diego, Oct. 4th to the 8th.
The posters describe clinical findings that highlight the key changes to
the human microbiome profiles of patients who received RBX2660, Rebotix’s Phase 3 drug candidate.
For the first time, researchers will discuss findings from the open-label Phase 2 trial of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff.) infection. Data indicated that RBX2660 was well tolerated and achieved the primary efficacy endpoint of preventing C. diff. recurrence; patients treated with RBX2660 exhibited a treatment success rate of 78.8% compared with a historical control of 51.8% (p<0.0001, N=242). These results demonstrate a 55% reduction in recurrence for those patients treated with RBX2660 compared to the historical controls reflecting standard-of-care antibiotics today.
RBX2660 is currently being evaluated in a multinational Phase 3 clinical trial for the prevention of recurrent C. diff. Researchers will also be presenting two posters on the microbiome analyses of the Phase 2B randomized, placebo-controlled, double-blind clinical trial of RBX2660. The analyses, utilizing leading edge genomic sequencing technology to measure the patient’s microbiome, provide measurable evidence of RBX2660’s rehabilitative effect on human microbiome profiles of patients who were successfully treated with Rebiotix’s microbiota drug technology.
“The clinical potential of RBX2660 has been highlighted in multiple trials, including our recently
completed open-label Phase 2 study, and the data being presented at ID Week enables us to more fully understand RBX2660’s ability to rehabilitate a dysbiotic intestinal microbiome,” commented Lee Jones, president and CEO of Rebiotix. “These findings are important in that not only can we observe the clinical 2 effect of RB X2660, such as in the open-label Phase 2 study, but by analyzing the microbiota of RBX2660-treated patients, we can see how the microbiome changes in response to RBX2660 treatment and how those changes correlate to treatment success and to the microbiomes of healthy individuals.”
The first poster (#1863; to be presented Friday, Oct. 6th), titled RBX2660 is Safe, Superior to Antibiotic- Treated Controls for Preventing Recurrent Clostridium difficile, and May Rehabilitate Patient Microbiomes: Open Label Trial Results, reported data from an open-label Phase 2 study of RBX2660 that included 242 subjects. Data from the study indicated that RBX2660’s efficacy in preventing recurrent Clostridium difficile infection (rCDI) was higher (78.8%) than CDI-free rates in the Historical Control Group (51.8%, p<0.0001). The reduction in recurrence of C. diff between these two arms is approximately 55%. Moreover, the safety profile of RBX2660 was consistent with results from previous clinical trials, and microbiota analysis suggested that RBX2660 may rehabilitate patient microbiota as RBX2660-treated subjects’ microbiomes were significantly altered compared to baseline and more closely resembled the RBX2660 microbiome profile than at baseline (p<0.05 by Dirichlet multinomial Wald-type pairwise hypothesis test).
The second poster (#1267; to be presented Saturday, Oct, 7th), titled Successful Response to
Microbiota-Based Drug RBX2660 in Patients with Recurrent Clostridium Difficile Infection is Associated with More Pronounced Alterations in Microbiome Profile, involved an analysis of 58 patients whose stool samples were collected in the randomized Phase 2B clinical trial to determine the effect of RBX2660 on rCDI patient microbiomes. 16s RNA sequencing analyses of patients’ microbiomes indicated that RBX2660 treatment shifted the relative microbiome densities, with taxa-specific increase in Bacteroidia, Clostridia, and decrease in Gamma-proteobacteria abundance. Importantly, a larger shift from baseline microbiome was seen in responders to RBX2600 compared to non-responders, and RBX2660 treatment appears to increase microbiome diversity.
The third poster (#1870; to be presented Saturday, Oct. 7th), titled Microbiome Profile is Distinct in Patients with Successful Response to Microbiota-Based Drug RBX2660 Relative to Placebo Responders involved a sub-analysis of 57 patients who participated in the randomized Phase 2B clinical trial of RBX2660. 16s rRNA sequencing analysis was used to compare the microbiome changes from baseline of patients classified as responders to RBX2660 vs placebo. Investigators determined that RBX2660 treatment for rCDI is associated with greater changes in patient microbiomes than placebo treatment. Notably, at 7, 30 and 60 days, microbiomes from RBX2660-treated patients had high Kullback-Leibler divergence from baseline and significantly different means from baseline (p<0.001). Further, active responders trended toward higher Bacteroides and lower Gamma-proteobacteria and Bacilli after treatment, both of which are characteristic of a healthier microbiome. According to the 3 researchers, these changes are consistent with the hypothesis that RBX2660 can restore a healthier microbiome in rCDI patients.