Lee Jones is the founder and CEO of Rebiotix Inc. a biotechnology company founded to revolutionize the treatment of challenging gastrointestinal diseases by harnessing the power of the human microbiome. The company has developed a unique biopharmaceutical platform called Microbiota Restoration Therapy (MRT) to restore healthy gut flora through the transplantation of live human-derived microorganisms. With a goal of furthering evidence-based knowledge of MRT through a structured clinical research program, Rebiotix recently completed enrollment in the PUNCH™ CD study, designed to assess the safety of RBX2660 (microbiota suspension) for the treatment of recurrent C diff infection. Delivered via enema, RBX2660, is streamlining delivery of the therapy for both patients and physicians. The company’s goal is to make this therapy widely available and as easy to use as a flu vaccine. Rebiotix is currently working on a protocol for a randomized multicenter study to further evaluate this new therapy. We are very grateful that Lee Jones has taken the time to answer our questions so that patients can be kept abreast of developments in the new and exciting industry of microbiome manipulation.
How are the clinical trials of your fecal microbiota product going? What are the success rates?
The PUNCH CD trial, which was a Phase 2 open label safety and preliminary efficacy study, was successfully completed in July 2014. An open label study means everyone enrolled in the study got the treatment and it is generally the first phase of a new product development program. The study demonstrated a success rate of 87% for those treated with no serious adverse events related to either the product or the method of delivery.
The PUNCH CD 2 study is now open for enrollment and Rebiotix is actively recruiting patients. The Punch CD 2 study is a multi-center, randomized, double-blind placebo-controlled trial of Rebiotix lead candidate RBX2660 (microbiota suspension) for the treatment of recurrent Clostridium difficile (C. diff.) infection and represents the most rigorous clinical study of fecal transplants to date. In this study, the patients may get the microbiota-based drug or may get a placebo. Neither the doctor nor the patients know what treatment is received in order to get an unbiased measurement of the drug’s true effectiveness. The PUNCH CD 2 study follows quickly on the heels of Rebiotix’s successful PUNCH CD study.
If the trials are successful, how long will it take to get the product to market? When will we be able to go to a pharmacy and buy it?
This is a good question. We will have to do one or more additional studies to meet the FDA requirements and then apply for licensure from the U.S. Food and Drug Administration (FDA). We don’t know how long it will take, but estimate at least 2 years.
Does your product have the full range of microbiota in the human gut?
We do not know if we have captured all of the microbiota in the gut in our product. We have tried for a formulation as close as we can measure to fresh fecal material because we know from historical results that using fresh material has been promising.
Who are the donors and how do you test them?
The donors are a variety of people that we know or have met through referrals. We test the donor and every donation according to a list of tests required by the FDA.
What makes your product the best option to treat diff.?
Our product has been tested in people who have had at least three episodes of C. diff. (or two if they have serious disease and were hospitalized in both cases) and who have failed standard treatments. We have never tested our product in a patient who is experiencing their first episode of C. diff. I can’t say that our product is the best option to treat the disease. But if we show that it is safe and effective in multi-recurrent patients, we hope that it will be recognized as one of the treatment options for those patients.
How many treatments are diff. patients likely to need with your product?
We have early evidence that some patients will do well on one dose and some will need two. It is very patient dependent.
What kind of patient prep is needed prior to using your product?
Patients who were in the trial were required to stop their antibiotic therapy one to two days before treatment. They were not required to undergo any other prep. We monitored the time of their last bowel movement before treatment with our product.
How much do you expect it to cost?
The price of the product has not yet been determined.
How will it be sold, as a capsule, enema – or both?
At this time we are testing it in an enema format. This method was chosen among the historical methods of delivery for being simple to do and having the fewest documented procedure-related complications. We have no experience with an oral product.
Are you proposing to extend trials to other conditions such as IBD or autoimmune illness?
We are exploring other conditions where our product might be useful.
Several companies are developing microbiome modulators which appear to promote the growth of specific colonic bacteria. Have you considered adding a “microbiome modulator” or a “prebiotic” to assist in the growth of the new bacteria after administered?
I think this is a good concept. We have considered a number of options for new products.
One of the risks cited regarding FMT is that it may trigger autoimmune illness, as well as cure it. Do you have a view on this?
I don’t know about connection with autoimmune diseases. The gut microbes play a big role in human immunological processes. There have been some reports in the literature of patients experiencing a flare of IBD or IBS after treatment. I think that this is where systematic collection of clinical data is so important. This data will help calibrate and identify the risks.
Opinions differ amongst clinicians regarding donor testing. The minimum we recommend at PoP is what is stated in the ISDA guidelines. However, some patients are concerned this is not enough. Do you believe there is benefit in standard metagenomic sequencing tests for donors? Will your donors and product be tested over time for viruses/ parasites/ fungi/ prions and antibiotic resistant bacteria?
Some of this testing is already being done and some of it is not for a variety of reasons – it could be impractical, too costly for the perceived risk, lack of a test – all sorts of things. I do believe that this is an area where it is easy to speculate about all the things that could happen because collectively we have great imaginations and we are smart people. Will those things actually matter or be a real risk? I don’t know. The American Gastroenterological Association and collaborators are working on establishing an FMT registry to help answer questions about donor screening.
Is there information circulating among the FMT community which you believe is incorrect or dangerous? How much consensus is there among the professionals researching FMT? What areas of difference are emerging within the medical-scientific community?
I think that the most dangerous thought about FMT that is circulating among people is that it can and should be used to treat everything and everyone. The professionals researching the topic have generally recognized that FMT can be an effective therapy for patients suffering from recurrent C. diff. but they also believe that it is too early and that not enough data exists to claim it can be used effectively for other problems, including inflammatory bowel disease (IBD). There is excitement and hope among the researchers that gut microbiota can make a difference in clinical practice. They just need time to figure out how and where.
Can fake poop ever be as effective as the real deal? Or could it be better – might we one day see “Super Poop” that combines the best elements of a healthy gut?
I don’t know the answer to this question. If by fake poop you mean a made up mix of microbes, viruses, fungi, nutrients, etc – it is possible. Again it depends on what the goal of creating the mix might be and what outcome one is looking for.
Is there anything else you would like to add?
Personally, I find the possibilities of using the human microbiome – our own ecosystem – to treat disease incredibly exciting and can hardly wait to see what the future has in store. I would also like to add that we are very excited about the progress we are making and would invite your readers to learn more about our work by visiting our website.
If you have recurrent Clostridium Difficile infection and would like to ascertain your eligibility for participation in the Punch CD 2 clinical trial and see the clinic locations, visit the Rebiotix website.