As far back as fourth-century China, people have used treatments that target the microbiome, or the trillions of organisms living in and on the human body. The Chinese used an off-putting, but effective soupy fecal-based concoction to treat severe food poisoning. In other eras and places, patients employed a similar strategy to treat dysentery and colitis.
A growing body of research shows the therapeutic potential of rebalancing the body’s communities of microscopic bugs, which play a critical role in everything from food metabolism and drug response to immune function and brain health. The gut, in particular, is heavily populated with organisms introduced by the mother at birth and later shaped and modified by the environment, medication and diet, among other factors.
Now approaches targeting these complex communities of organisms are gaining further traction in pharma.
The human body contains more foreign microbes than human cells and each of these living collectives is unique to the individual. Some people have healthier groupings than others. When the balance of organisms is askew, called dysbiosis, it contributes to disease.
In November 2022, the FDA approved the first microbiome-based treatment, Ferring Pharmaceuticals’ Rebyota. The second, Vowst, from Seres Therapeutics, in collaboration with Nestlé Health Science, got the nod last April. Both treat Clostridioides difficile (C. diff), which sickens 500,000 people each year, killing roughly 30,000. These approvals may usher in what IQVIA called a new era in microbiome-based medicines.
While indications for gut-based conditions remain a priority target, researchers are also exploring a microbiome-based approach for a broad spectrum of diseases from multiple sclerosis, inflammatory bowel disease and cancer to mental health conditions, autism, Alzheimer’s disease and even substance use disorders. The market could reach $434 million by 2025.
The impact of emerging meds
Like many of its earliest predecessors, Rebyota uses a donor-derived, fecal-based approach to modify the mix of organisms in the intestines. Vowst took a different tact, isolating spores from donated human feces and putting them in an oral capsule. Patients can take the medication at home after a course of antibiotics to prevent a recurrence.
“Previously, treatment options for recurrent C. diff were limited and focused on continued treatment with antibiotics and, in some cases, rectal administration of fecal microbiota that work to repopulate the gut microbiome,” said Moreno Perugini, president of Active & Medical Nutrition and Global Pharmaceutical Therapies, Nestlé Health Science. “These therapies are not FDA-approved, generally have investigational status, and only available in certain healthcare facilities.”
In studies, 88% of people taking four daily capsules of Vowst avoided C. diff reinfections after eight weeks compared with 60% of people who took the placebo. After six months, 79% of the treatment group were still reinfection-free compared with just over half of the placebo group.
“Microbiome therapeutics like Vowst have the potential to change how we manage certain diseases by considering the complex interactions between the individual and gut microbiome,” Perugini said. “Through targeted modulation of the gut microbiome, there is the possibility of influencing metabolic processes and immune activities ultimately addressing patients’ unmet needs.”
While Vowst is currently approved to prevent C. diff recurrence, applications could multiply.
“Through targeted modulation of the gut microbiome, there is the possibility of influencing metabolic processes and immune activities ultimately addressing patients’ unmet needs.”
President, Active & Medical Nutrition and Global Pharmaceutical Therapies, Nestlé Health Science
“As part of our commitment to patients, we continuously evaluate opportunities for expansion, whether through new indications or reaching different patient populations affected by C. diff. Alterations in the gut microbiome have been associated with several gastrointestinal and non-GI conditions. The team is exploring the potential of Vowst in these disorders, understanding that more clinical research is needed,” Perugini said.
Now, researchers could target colitis and diarrhea not caused by C. diff. with microbiome therapies.
“The GI space holds significant interest for Nestlé Health Science, given our extensive expertise in GI and nutrition. We are dedicated to expanding our presence in this therapeutic category,” Perugini said.
Big Pharma gives microbiomes a look
Other companies, such as Johnson & Johnson Innovative Medicine, Takeda and Pfizer, have also taken tentative steps into the microbiome therapeutics market, according to IQVIA. Because the field is new and risky, larger companies are sometimes forgoing acquisitions and instead backing research so they can see if it will pan out.
And the space now boasts more than 220 microbiome tech companies, along with 700 active programs, according to the Microbiome Therapeutics Innovations Group. Gut-based conditions remain a prime target for R&D.
Vedanta Biosciences has treatments in the clinic for C. diff, inflammatory bowel disease and food allergies, as well as one for gram-negative infections approaching clinical research.
Others are looking at organs throughout the body.
Luca Biologics, a biotechnology company spun out from Seed Health, a microbial sciences company accelerating breakthrough science into live biotherapeutics, is developing microbiome treatments for common women’s health conditions including urinary tract infections (UTIs), a common vaginal infection called bacterial vaginosis, and preterm births. The company expects to initiate a phase 1b trial for its UTI treatment sometime this year.
Seed Health is also collaborating with Axial Therapeutics to develop microbiome drugs to treat mental health conditions, including anxiety and depression. Axial is focused on irritability associated with Autism, Parkinson’s, cancer and nonalcoholic steatohepatitis (NASH).
MaaT Pharma has treatments in its pipeline aimed at diseases such as amyotrophic lateral sclerosis, which is marked by numerous changes in the microbiome, and oncology. Because the microbiome can affect how well patients respond to checkpoint inhibitor cancer drugs, one of its investigational treatments aims to alter the microbiome to improve outcomes.
While much of this research is still in the early stages, this R&D momentum will help pharma gain a more comprehensive understanding of the interplay between the trillions of microbes from 1,000 different species, how they drive disease and how to modify them to improve human health.