Twin Cities biotech start-up Rebiotix has treated its first patient in what the company hopes will be the last leg of the race to develop the first approved microbial therapy derived from human waste to treat serious infections from the bacterium Clostridium difficile.
"C. diff," as it usually known, colonizes the large intestines of about 500,000 people per year, often after antibiotic treatments in hospitals, leading to the deaths of more than 29,000 people annually. For several years, Roseville-based Rebiotix has been in competition with a Massachusetts-based firm to develop the first therapy that can treat recurrent C. diff infections by restoring the natural ecosystem of microorganisms in the intestine.
On Aug. 7, Rebiotix announced that it had enrolled the first of a planned 270 patients in a double-blind, placebo-controlled randomized clinical trial intended to show microorganisms in stool donations from Twin Cities residents can be used to safely and effectively treat C. diff infections.
The Phase III trial is slated to end in 2019, which is when Rebiotix is aiming to get final approval of its biologic drug product. Cambridge, Mass.-based Seres Therapeutics, which is developing a similar therapy, is scheduled to conclude a major clinical trial of its product around the same time.
"I believe this is a transformational technology," Rebiotix founder and CEO Lee Jones said Friday.
The human gut is home to billions of bacteria and other microbes that together form a kind of ecosystem known as a "microbiome," which provides a variety of critical functions for human survival that are still being puzzled out by scientists, according to the National Institutes of Health's Human Microbiome Project.
Although everyone carries around microscopic pathogens in their bodies, these microorganisms coexist with their host and the rest of the microbiome without causing disease in healthy people. Researchers at the NIH and other organizations are working to understand why and how some pathogens end up causing disease in some people.
C. diff is one of the organisms that may live in a person's intestines, though it is also spread via food and contaminated surfaces. Taking powerful antibiotics in the hospital, particularly by older patients, can kill off a wide swath of the organisms in the gut microbiome and create the opportunity for C. diff to grow out of control and colonize the large intestine. The result can be a nasty infection that causes dayslong bouts of watery diarrhea and abdominal cramping.
The mainline treatment for C. diff is to give more antibiotics, but this can lead to a cycle of recurrent infections. At least 20 percent of patients with a C. diff infection go on to have at least one other episode, which can turn deadly in extreme cases.
Rebiotix has been on the hunt for a different therapy, in which the gut-microbiome organisms from one person are transplanted into another person.
Jones said the company has a coterie of paid donors from the Twin Cities who come to the office in Roseville several times a week to donate samples. The samples are kept separate for quality control and are rigorously tested before being processed into biologic drugs.
Unlike Seres Therapeutics, which is testing a therapy of introducing specific microbes into the gut, Rebiotix aims to preserve the natural diversity of microorganisms from its donors.
"Our product is the first of its kind," Jones said. "We try to keep as many microbes alive, in as much diversity as we can. The goal is to be able to restore a sick person's gastrointestinal microbial community, which helps treat their disease as well as fight off new diseases."
Candidates for the clinical trial of Rebiotix' product, known by the generic name "RBX2660" for the time being, must have had a C. diff infection plus at least two subsequent reinfections. The multicenter trial will compare patients getting RBX2660 to those getting a blinded placebo to see whether the drug cuts down on the proportion of patients who have infections eight weeks after treatment. RBX2660 has already been validated in several early-stage clinical trials.
Founded in 2011, Rebiotix is a pre-revenue company with 32 employees and has raised $30 million thus far from local investors who took advantage of the state's Angel Tax Credit program.
"We're pretty much a homegrown company, with homegrown investors and homegrown people here from Minnesota," Jones said.