Investigational Oral Biologic Achieves 100% C difficile Clinical Cure in Preliminary Cohort
Lumen Bioscience’s, LMN-201, was considered safe and well-tolerated and there were no severe dose-related or serious adverse events reported.
Today, Lumen Bioscience reported that its investigational oral biologic, LMN-201, achieved a 100% clinical cure rate of C difficile infection (CDI) in the sentinel cohort (Part A) of its RePreve clinical trial. All patients (21/21; 95% confidence interval [CI]: 85%-100%) achieved initial clinical resolution, significantly outperforming (p << 0.001) the 80% initial clinical cure rate (625/781; 95% CI: 77%-83%) observed in the active arm of the large MODIFY I and II studies.1
“Seeing zero failures after initial combination treatments and a low recurrence rate in this high-risk group is extremely encouraging. It suggests that LMN-201’s tandem mechanism—targeting both the C difficile bacterium and its toxin—can improve outcomes, as it did in preclinical studies,” George McDonald, MD, emeritus professor of Medicine at the University of Washington, said in a statement.1
McDonald acknowledges the small cohort size but notes that the clinical cure rate is a rarity. “While our sample size is limited, such an outcome gives us confidence as we move forward,” he said. “It’s a promising sign, suggesting that LMN-201 could significantly improve patient outcomes and reduce recurrence—the holy grail in C difficile management.”1
Only 1 of 21 patients (4.76%; 95% CI: 0.24%-23%) who completed 7 days of standard-of-care (SoC) plus LMN-201 experienced CDI recurrence within 28 days, compared to 161 of 621 patients (26%; 95% CI: 23%-30%) who experienced recurrence after SoC alone in MODIFY I/II, and 87 of 625 patients (14%; 95% CI: 11%-17%) after SoC plus bezlotoxumab treatment in MODIFY I/II within the same time period. Of the 21 subjects in the RePreve Trial sentinel cohort who completed seven days of LMN-201, 16 received vancomycin, 4 fidaxomicin, and 1 metronidazole.1
LMN-201 is delivered in capsules and is intended for use with and following antibiotics to improve clinical outcomes for C difficile infection. It is made with Lumen’s proprietary spirulina-based GMP manufacturing system. In a previous interview with Contagion, Lumen Bioscience cofounder and CEO Brian Finrow explained that LMN-201 was developed based on former research from Mass Bio and Merck on the creation of an antibody against C difficile.1,2
“What they found is that if you make an antibody against the C. difficile toxin—the disease in humans is mediated by this toxin called toxin B—if you make an antibody, it'll neutralize the toxins just like snake antivenom,” Finrow said.2
The images depict the conventional monoclonal antibody approach and how Lumen's LMN-201 is delivered and destroys C diff cells.
Image credit: Lumen Bioscience
These sentinel cohort results were achieved with only seven days of dosing. In the RePreve Trial’s main cohort (Part B), the LMN-201 dosing window will increase from seven days to approximately 70 days (until eight weeks after initial clinical cure). This extended treatment duration aims to provide protection throughout the period of greatest risk for CDI recurrence: the weeks immediately after antibiotic use when the healthy commensal microbiome naturally re-engrafts.1
With the sentinel cohort now completed, Lumen has begun Part B (the main cohort). This pivotal phase is a randomized, double-blind, placebo-controlled study that will enroll approximately 350 patients at research centers across the U.S. Participants will be randomized 1:1 to receive either LMN-201 or a placebo—each alongside standard antibiotic therapy—to rigorously evaluate the drug’s efficacy in a larger population. The primary endpoint is “sustained clinical cure” (initial clinical cure plus no recurrence at 12 weeks) relative to placebo.1
The RePreve Trial main cohort is now recruiting.For investigators and potential participants interested in participating, they can email trials@lumen.bio or visit the official RePreve study webpage.
