Improvement of MICROBIOME HEALTH INDEX™ in Patients with Recurrent Clostridioides difficile Infections Following RBX2660 Treatment is Associated with a Reduction in Antimicrobial Resistance Genes

Courtney Jones BS, Ken Blount PhD, Tonya Ward PhD, Elena Deych MS, Bill Shannon PhD, MBA

Background

• RBX2660, a standardized, stabilized microbiota restoration drug has been shown to prevent recurrent Clostridiodies difficile infections (rCDI).
• A preliminary analysis demonstrated decolonization of multidrug-resistant organisms (MDRO) in association with clinical response.
• In parallel, we are developing a MICROBIOME HEALTH INDEX™ (MHI™) to monitor dysbiosis and microbiome restoration.
• Given the public health challenges related with MDROs, we evaluated MHI as a potential sentinel of MDRO colonization among rCDI patients who responded to RBX2660 in a Phase 2 clinical trial.

Methods

• The PUNCH CD2 Phase 2 trial (NCT02299570) compared RBX2660, a microbiota-based investigational drug for treatment of rCDI, to placebo.
• 127 participants were enrolled, randomized, and treated in three cohorts: Group A: two doses of RBX2660; Group B, two placebo doses; Group C, one dose of RBX2660 and one dose of placebo.
• Samples were collected prior to treatment (BL) and 7, 30 & 60 days after treatment.
• This analysis is based on samples from 55 patients who responded to RBX2660 treatment in Groups A and B (pooled) and dosed RBX2660 product samples.
• Stool samples were sequenced using BoosterShot (CoreBiome, Minneapolis, MN), an ultra-shallow shotgun sequencing method.
• MICROBIOME HEALTH INDEX™ (MHI™) values were calculated based on relative abundances at the class level for selected classes.
• Prior receiver operator characteristic analyses defined an MHI cut-point of 8.2 for distinguishing rCDI subjects prior to treatment from the representative microbiome composition of RBX2660.
• Relative abundance of antimicrobial resistance (AMR) genes and enzymes were determined for all samples based on a threshold of ≥ 90% coverage when compared to the MEGARes database .

RBX2660 Efficacy in a Phase 2 Controlled Trial

• See poster (401 KB)

Microbiome Composition Shifts Post-RBX2660

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MICROBIOME HEALTH INDEX™ (MHI™) Analysis

• See poster (401 KB)

Relationship Between MHI and Antimicrobial Resistance Genes

• See poster (401 KB)

Conclusions

• MHI can effectively distinguish patients with dysbiosis from healthier patients, as defined by the RBX2660 product profile and the Human Microbiome Project.
• MHI inversely correlates with AMR gene abundance in a cohort of rCDI patients who had successful response to RBX2660.
• These results suggest MHI as a potential sentinel of MDRO colonization, and this role will be evaluated in future cohorts outside of the rCDI patient population.