LOS ANGELES—Ritter Pharmaceuticals, Inc., a developer of novel therapeutic products that modulate the human gut microbiome to treat gastrointestinal diseases, has announced that clinical microbiome data from its Phase 2a clinical trial of RP-G28 in patients with lactose intolerance were published in the Proceedings of the National Academy of Science (“PNAS-Plus”) online ahead of print Jan. 3.
DDNews spoke to Andrew Ritter, co-founder and president of Ritter Pharmaceuticals, who says, “RP-G28 is a galactooligosaccharide—a non-digestible carbohydrate—a prebiotic. Prebiotics are fibrous components that feed the bacteria in your colon. They stimulate the growth of certain bacteria in the digestive tract. So when you consume a dairy product, these bacteria will be more robust and will help consume the lactose.”
The paper, titled “Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals,” reports findings on RP-G28, the company’s lead therapeutic candidate, which is a short-chain galactooligosaccharide (GOS). The data validates RP-G28’s mechanism of action and supports the product as a potential treatment for lactose intolerance. The newly published microbiome data provides further insight into RP-G28’s Phase 2a 2013 clinical trial, which has led to a Phase 2b/3 377-subject clinical trial.
Ritter says the Phase 2b/3 study is currently ongoing—the last patient completed the program in the study in the last quarter of 2016. “We anticipate having topline results released in the first quarter of 2017, after we’re finished finalizing and unblinding the data. Once the results are announced and we further finalize our review of the clinical program, our plan is to meet with the FDA for feedback, and at some point in this process we will look to publish this data in a respected journal.”
The results of the study demonstrated that RP-G28 significantly modulated the gut microbiome composition of lactose intolerant individuals. Significant changes in the diversity of the microbiota occurred in GOS/RP-G28 treated subjects upon reintroduction of dairy into the diet. Key bacterial taxa changes included increases in lactose-fermenting Bifidobacterium, Lactobacillus and Faecalibacterium, and those changes correlated with a symptomatic improvement in tolerance to lactose (the sugar present in dairy foods). Notably, 90 percent of the RP-G28 treatment group showed a bifidogenic response compared to other GOS studies, which reported a bifidogenic response in 50 percent of the treated subjects.
Asked about how RP-G28 performs best, Ritter says, “A patient takes the product for 30 consecutive days. Then, after dairy is reintroduced into their diet, they gain the ability to tolerate dairy products, and have reduced or eliminated symptoms. As we’ve seen in our clinical trials, the microbiome continues to show a change that maintained or increased these lactose bacteria, at least 30 days after treatment. We’ll be tracking patients for 12 months to see how they do.”
The study was a multicenter, randomized, double-blinded, placebo-controlled Phase 2a trial to evaluate whether a shift occurred in the fecal microbiome of lactose-intolerant human subjects who were treated with RP-G28 and a dairy diet and who exhibited a clinical response toward lactose tolerance.
The study evaluated a patient’s ability to consume dairy foods after first feeding RP-G28 for 35 days, followed by 30 days of introducing dairy products into the diet. A total of 85 subjects were enrolled in the trial with 57 randomized to receive RP-G28 and 28 in the placebo group. Dr. Andrea Azcarate-Peril, director of the Microbiome Core Facility at the University of North Carolina, Chapel Hill, School of Medicine, and Distinguished University Professor Dr. Todd Klaenhammer, of the Department of Food, Bioprocessing & Nutrition Sciences at North Carolina State University, Raleigh, conducted the analysis.
Ritter, who developed Ritter Pharmaceuticals specifically to solve the issue of lactose intolerance, originally used himself as the first test subject. Twenty years after first taking a GOS, he reports that he is symptom-free. He developed a first generation of products, which he says 15,000 people used. He says, “80 percent of those people reported improvements and maintained tolerance, after tracking them for over three years.”
Now, Ritter is building on that initial success. “The product can technically be sold OTC [over the counter], but because we’re going after FDA claims, we’re going through the approval process to garner more credibility as a prescription drug,” Ritter says.
Azcarate-Peril added, “This is a seminal study producing some of the first data in lactose intolerance showing the microbiome’s role in being able to metabolize lactose independent of host enzymes. Furthermore, it’s remarkable that we observed a definitive shift to being lactose tolerant after a single 35-day dosing of RP-G28.”
The microbiome analysis also uncovered other potentially health-promoting bacteria, specifically Faecalibacterium, that were enhanced by feeding RP-G28. This suggests that RP-G28 might have potential therapeutic benefits in inflammatory bowel disease and metabolic syndrome, among other diseases.
“We’re starting to explore, with lactose intolerance, how you can make shifts and changes in the gut microbiome. If you can change the microflora in your colon, you can have certain health benefits besides just lactose tolerance,” Ritter says. “We’re beginning to explore to see how our treatment might be able to help other diseases. We’re taking the principles of how we deal with lactose intolerance, and using it to explore other applications.”
