In just a few short years, Rebiotix has taken the concept of “bugs as drugs” and turned it into actual practice, constructing a standardized, stabilized drug product from the broad consortia of microbes present in a healthy person’s intestinal tract, including developing analytical methods and a consistent and scalable manufacturing process, something which had never been done before. The company has also generated some of the largest clinical datasets in the world showing safety and efficacy of this class of product, all of which has been under FDA-approved clinical trials.
Ken Blount, Chief Scientific Officer at Rebiotix gave us his thoughts on developing microbiome therapies; the challenges involved, regulatory affairs and where he sees the future of microbiome research.
Rebiotix has one of the most advanced human clinical program evaluating a microbiota-based drug. Can you tell us some of the challenges you faced along the way?
The list of hurdles that we had to overcome is long. In the beginning of this industry, there were core challenges that needed to be addressed before we could even consider using this therapy in a clinical trial. First, the manufacturing process had to be standardized and quality controlled – there were dozens of ways in the literature that stool-based therapies were being generated, mostly from very small studies, and none of them showed the stability, standardization or release criteria that would normally be required for a pharmaceutical-grade product. Additionally, there was no standardized donor testing and recruitment program; this is critical to the safety of the product, so we spent a lot of time and resources working through this. Since there was no precedent for donor testing or product manufacturing, there was no regulatory guidance either – to say that it has been a learning experience for both us and the FDA would be an understatement! Lastly, there was – and still is – a lot of misinformation about the abilities of the microbiome to treat therapies, which has led to a lot of unregulated product manufacture and use. We’ve seen the “DIY” or uncontrolled production of stool-based material skyrocket based on misinformation, and it has made educating physicians and patients about the value of controlled clinical trials challenging.
Our approach has been to work with the FDA from the beginning, and to document our entire development and manufacturing process under Good Manufacturing Practice standards. We also work with key opinion leaders to design well-controlled clinical studies to ensure that the safety and efficacy data we collect is verifiable. All of this will ultimately support the validated safety and efficacy outcomes of our product for patients once this drug product is commercially available.
At what stage do you think you should approach regulatory authorities and what advice would you give other biotechs looking to get help with regulation?
There is a misconception that regulation stops or hinders innovation – this has not been our experience. We went to the FDA early in our development pipeline to discuss our product ideas and clinical trial proposals, which allowed them to really dig into the details of our data. This supports our mutual goal of understanding product safety to protect the patient, and it also has allowed both groups to stay informed on this fast-moving product landscape. We highly recommend engaging with regulators like the FDA early in a biotech company’s lifetime, as it will ensure that the company stays in line with regulations and it assures that the FDA is fully aware of company progress. This will result in a better product for the patient.
Can you summarise how the Microbiota Restoration Therapy (MRT™) Drug Platform works?
All of us carry a complex ecosystem of microbes in our gut. This ecosystem helps us perform a variety of functions, from digesting food to preventing illness. If this ecosystem is damaged, it is possible for pathogens take over or injury to occur that then makes us sick. The MRT™ platform is based on the principle that if we can restore a damaged microbial ecosystem, we can restore a person’s ability to keep themselves healthy…the best way to do this is by collecting a broad consortium of microbes from healthy donors. We do this through a standardized, quality-controlled process to make sure we are delivering the same product to each patient – this is important because it allows us to learn about the restorative effects of our products very quickly. We have directly quantified restoration in the microbiomes of patients treated to prevent recurrent Clostridium difficile infection, and it has helped us form hypotheses about how the MRT platform will work in other indications.
What advice would you give biotechs beginning to develop therapeutics in the microbiome space right now?
The microbiome space is constantly growing and changing – those that bring creativity to the table (backed by science and clinical evidence) will be the ones driving innovation. Additionally, biotechs that can form partnerships with good teams and key opinion leaders will learn faster than those that try to go it alone.
A lot of progress has been made with C.diff. However, you are also looking into UC, Drug resistant UTI and Hepatic Encephalopathy. Which disease do you think will be the most responsive to microbiome based therapeutics?
It’s hard to say at this point because each of the disease states are so different. There is some literature and some anecdotal evidence showing that all of them have potential depending on the duration of therapy and the presentation of the disease. This is why we are partnering with high quality investigators and industry partners to make sure that we completely understand the disease states before we start giving our therapies to patients.
How do you see future of microbiome research evolving?
We are only seeing the “tip of the iceberg” in terms of the potential of the microbiome. There will be new products, new analytical methods, and new supportive technologies that will completely change the way we approach medicine. This will not be a fast process, but it is already happening – the difference between the industry today and the industry a year ago is immense.
Without giving away your trade secrets what are your next steps?
We are continuing to look at the connection between patterns of changes in the microbiome (like a biomarker) and clinical outcomes. This is critical to understand what influence the microbiome, its functions, or specific microbes have over human health. We are also pursuing clinical trials in indications outside of infectious disease, which promises to be very exciting.