Lumen has officially published top-line results from the sentinel cohort of its RePreve Clinical Trial which evaluated LMN-201 for Clostridioides difficile infection (CDI).
In case you weren’t aware, LMN-201 is an oral biologic assortment which, delivered in capsules, is designed for use with and following antibiotics to improve clinical outcomes for C. difficile infection. More on the same would reveal how this particular drug relies upon Lumen’s proprietary spirulina-based GMP manufacturing system.
Anyway, talk about the published results on a slightly deeper level, we begin from how the drug was able to a achieve 100% initial clinical cure: You see, all 21 patients would go on to complete 7 days of LMN-201 plus standard of care (SoC) antibiotics (metronidazole, vancomycin, or fidaxomicin). This translates to how the drug significantly outperformed (p<<0.001) 80% initial clinical cure rate (625/781; 95% CI 77-83%) observed in the active arm of the large MODIFY I and II studies.
You see, the RePreve Trial was markedly designed to facilitate comparisons to the MODIFY trial, which targeted the same patient population with the same SoC antibiotics, combined with the IV-infused monoclonal antibody, bezlotoxumab. Patient demographics were also similar between RePreve and MODIFY I/II.
“We are pleased that LMN-201 appears to be safe and well-tolerated in patients,” said Brian Finrow, CEO and co-founder of Lumen. “This was our first opportunity to observe LMN-201’s effects in a clinical setting, in patients with active C. diff, and the absence of dose-related adverse events is reassuring. We can now proceed to the placebo-controlled phase with a solid foundation of safety and an encouraging preliminary efficacy signal. We look forward to confirming these results in the larger trial, which is recruiting now.”
Next up; we must dig into how LMN-201 would clock significantly enhanced 28-day sustained clinical cure. The sustained cure rates through Week 4 for SoC alone (MODIFY I/II), SoC plus LMN-201 (RePreve sentinel cohort) and SoC plus bezlotoxumab (MODIFY I/II) were 59.5% (460/773; 95% CI 56-63%), 95.2% (20/21; 95% CI 77-100%) and 68.9% (538/781; 95% CI 66-72%), respectively.
It must also be mentioned that the improvement in sustained cure through Week 4 between LMN-201 and SoC was 35.7% (p<<0.001), and if we look at LMN-201 and bezlotoxumab, the same improvement was 26.3% (p<0.001).
Another detail worth a mention here is rooted in the therapeutic’s successful bid to achieve a reduction in CDI recurrence. We get to say so because no more than 1 of 21 patients (4.76%; 95% CI 0.24-23%), completing seven days of SoC plus LMN-201, experienced CDI recurrence within 28 days.
To put things into perspective, 161 of 621 patients (26%; 95% CI 23-30%) observed recurrence after SoC alone in MODIFY I/II, whereas on the other hand, 87 of 625 (14%; 95% CI 11-17%) experienced the same after SoC plus bezlotoxumab treatment in MODIFY I/II in the same time period.
Among other things, we ought to mention how RePreve Trial has a two-part design. The Part A, which includes the Sentinel Cohort, was to confirm LMN-201’s safety in high-risk individuals with CDI, and to let Lumen optimize the trial infrastructure and patient recruiting.
Now, with the sentinel cohort successfully completed, Lumen has initiated proceedings of Part B (main cohort), a randomized, double-blind, placebo-controlled study that will enroll approximately 350 patients at research centers across the U.S. Here, participants will be randomized 1:1 to receive either LMN-201 or placebo, alongside standard antibiotic therapy in each case, to rigorously evaluate the drug’s efficacy across a larger population. The primary endpoint would be “sustained clinical cure.”
“The sentinel cohort data provide strong initial validation for our multi-component approach to CDI,” said Dr. George McDonald, Consultant to Lumen and Emeritus Professor of Medicine at the University of Washington. “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. diff bacterium and its toxin – can improve outcomes, as it did in preclinical studies. While our sample size is limited, such an outcome gives us confidence as we move forward. It’s a promising sign.”
