Rebiotix calls their microbiome drugs “Microbiota Restoration Therapy” (MRT). They are live, human-derived microbes, used to treat diseases and infections of the intestine. While RBX2660 is an enema, the company’s second drug candidate, RBX7455 is an oral prevention pill for C. diff infections. I’m assuming that “prevention” means they administer the drug along with antibiotics to prevent recurrence of C. diff in patients that already have C. diff. The novel thing about RBX7455 is that it is a lyophilized powder and does not require freezing or refrigeration, which makes it very easy to store in pharmacies as well as for patients to take home and administer to themselves. Other comparable drugs for C. diff will most likely require freezing, or at the least refrigeration; this adds another layer of complexity as everything from shipping to storing in clinics and pharmacies, to proper patient handling at home must be temperature controlled. RBX7455 has just entered Phase I clinical trials, which will be a small study of just 20 patients, but if it proves as promising as RBX2660, then this drug may also be put on the fast track to FDA approval.
Rebiotix is also developing an MRT called RBX2477 for hepatic encephalopathy, which is build of ammonia in the body due to failure by the liver to regulate ammonia in end-stage liver cirrhosis. RBX6376 is another MRT in development to target patients infected with multi-drug resistant organisms, such as vancomycin-resistant Enterococcus, which can result due to an overuse of vancomycin (often used to treat Clostridium difficile patients).
As with any live, microbe-based therapies, consistency in- and handling of- the drug product are important issues. Drug products that are directly derived from human-stool and rely on donations are a regulatory agency’s nightmare and require screening for many different pathogens. This is one of the reasons why FMTs are not yet FDA approved, and also why companies like OpenBiome, Rebiotix, and Seres Therapeutics go through extensive lengthy screening processes for all donations to be used in the clinic. After the initial screening, any products derived from human stool need to be consistently effective lot-to-lot, and because all stool is different even from the same donor on different days, consistency is a difficult metric to define, measure, and execute. Many companies for now are focusing on the end goal of transplanting and diversifying a patient’s dysbiotic microbiome, rather than worrying too much about lot consistency. A diverse intestinal microbiome seems to be the key point in defining success of a drug in treating infection, so as long as the drugs achieve this endpoint the drugs are likely to do better than placebo. Thus, while FMTs and enemas work fine for the time being to cure C. diff infections and recurrence, it’s very likely that someday these effective but relatively crude methods will be a thing of the past once live microbe-containing pills are able to be consistently manufactured and show efficacy in reaching endpoints. Rebiotix is on the right track with its pipeline, moving from enemas to pills.
Rebiotix also has a collaboration with McMaster Children’s Hospital to run a large clinical trial on pediatric patients with debilitating ulcerative colitis. This is a big step because more and more, pediatric patients are suffering from intestinal diseases that can stump their growth and development. Thus, treatments for minors are extremely important and Rebiotix is one of the only companies conducting clinical trials in this space.