A New “FMT” Probiotic to Treat Ulcerative Colitis: A Clinical Trial

The results of a stage 1 clinical trial of a novel probiotic (created from purified human stool) in treating mild to moderate ulcerative colitis (UC) were just published in the journal, Gastroenterology.[i]  I didn’t pay a huge amount of attention last week when I first spotted it, but decided to check it out this past weekend, in case there was anything useful for us.  It turned out there is, so I’m glad I took the time.

It appears that this product will be, at least at first, considered a pharmaceutical. There’s good and bad to that, of course:  the bad is that I’m afraid it will only be available via prescription and my guess is that, at least at first, it will only be covered by insurance for UC or perhaps, other inflammatory bowel diseases.  Those of us without will likely be out of luck in obtaining it.  The good is that for those who desperately need it, it will be covered by insurance and considering how expensive ordinary probiotics are, that’s not a bad thing. Still, this particular type of probiotic holds tremendous interest to, and promise, for all of us.

By the way, a quick aside:  I did find a 2019 press release stating that an upcoming late stage 2B trial was in the works and that this trial is considered pivotal in that, the Company (Seres Therapeutics) who manufactures the product, “…recently obtained feedback from the FDA indicating that the results from this study, in conjunction with data from a second pivotal study, could enable a SER-287 Biologics License Application.”[ii]

Still, as probiotic capsules or liquids created from isolated, purified bacteria from human stool will someday be par for the course (remember that just such a product was used in the very successful studies on autism.  Also, products, isolated from elite athletes, are also being created to improve athletic performance.  So even if the products are not as yet available to us mere mortals, I think we should follow along with the research as it piles up.

Back to the now published phase 1 trial to establish safety and efficacy: this was a double blind trial on 58 adults with mild to moderate UC.  They all received 6 days of either oral vancomycin (a gut antibiotic) or a placebo, and then 8 weeks of either the probiotic (SER-287) or a placebo. In total there were 4 groups:  placebo/placebo; placebo/SER-287 once per week; vancomycin/SER-287 once a week; vancomycin/SER-287 daily.

The results: “A higher proportion of patients in the vancomycin/SER-287 daily group (40%) achieved clinical remission at week 8 than patients in the placebo/placebo group (0), placebo/SER-287 weekly group (13.3%), or vancomycin/SER-287 weekly group (17.7%)…”  That’s a pretty outstanding result!  By the way, there were no differences in adverse events reported among the various groups.

It’s also important to note that they found higher levels of the species in the probiotic in stool from those on the probiotic versus those on a placebo, but in the group that did not get vancomycin first, this was not maintained after a week.  In those in the vanco groups, higher levels of SER-287 species were found in stool throughout the study compared to those who got the placebo (not vanco), and as you’d expect, the highest levels were found in those who got the probiotic daily.  In other words, the treatment did exactly as planned:  vancomycin wiped out much of the gut flora which was then successfully altered with the human-derived probiotic, which colonized the intestines leading to remission at a clinically significant rate.

Bear in mind that this was just a small, short phase 1 study too.  For all we know, the rate of remission might be higher if it had lasted longer.  Secondly, we also don’t know that optimal dosing was used yet.  (We also, of course, don’t know what the participants were eating during the trial.  Not relevant to this study.  Still, wouldn’t it be interesting to know that when comparing those 40% who achieved remission versus those 60% who did not?!) They conclude, therefore, that, “SER-287 following vancomycin was significantly more effective than placebo for induction of remission in patients with active mild-to-moderate UC.”

In case you were wondering how the probiotic was produced: the FDA approved their process for screening, and 3 stool donors were selected.  The stool was cleared of all impurities and 3 lots of SER-287 were produced, each lot from only 1 of the donors.  They basically pulled out some of the bacteria that are not spore-forming, so that each product ended up with 10-20% spores by weight, and included species like Clostridium, Gemminger, Dorea, Roseburia, Blautia, and Faecalibacterium.  After treatment, a decrease in non-spore-forming bacteria like 12 Veillonella, Streptococcus, and Bacteroides was noted.  Spore-forming bacteria tend to be quite resilient because, when in an inhospitable environment, they retreat into hardy spores, and can reactivate when circumstances improve.  (This is why C.difficile infections are so damn hard to eradicate.)

I am quite sure we are seeing the start of a trend:  treatment of disease by eradication of “faulty” bacterial microbiomes followed by replacement with healthy bacteria.  This is essentially non-invasive fecal microbiota transplant, but of course, with select species of bacteria.

I took a quick look at Seres Therapeutics website and found that they just released, in August, a press release announcing  positive results from a phase 3 trial of another product, SER-109, to treat recurring C.difficile infection (CDI), in fact.  “The study showed that SER-109 administration resulted in a highly statistically significant absolute decrease of 30.2% in the proportion of patients who experienced a recurrence in CDI within eight weeks of administration versus placebo, the study’s primary endpoint. 11.1% of patients administered SER-109 experienced a CDI recurrence, versus 41.3% of placebo patients.”  They are now applying for final product approval from the FDA.    Looks like this is a company we’ll have to keep an eye on!

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[i] as: Henn MR, O’Brien EJ, Diao L, Feagan BG, Sandborn WJ, Huttenhower C,Wortman JR, McGovern BH, Wang-Weigand S, Lichter DI, Chafee M, Ford CB, Bernardo P, Zhao P,Simmons S, Tomlinson A, Cook D, Pomerantz R, Misra BK, Auninš JG, Trucksis M, A Phase 1b safetystudy of SER-287, a spore-based microbiome therapeutic, for active mild to moderate ulcerative colitis,Gastroenterology (2020), doi: https://doi.org/10.1053/j.gastro.2020.07.048.

[ii] https://www.microbiometimes.com/seres-therapeutics-announces-initiation-of-ser-287-phase-2b-eco-reset-clinical-study-for-ulcerative-colitis/