• Gut health is linked to diseases ranging from cancer, diabetes, and depression
• 43% of microbiome-targeting therapies for infectious diseases are being investigated in Clostridioides difficile infections (CDIs)
• Data show that viral shedding of COVID-19 in stool samples persist much longer than in respiratory samples, potentially playing a role in long COVID
• Rebiotix is the strongest player, and will gain significant market share if both of its drugs, RBX-2660 and RBX-7455, are approved

Targeting the gut microbiome is a largely unexplored but quickly developing therapeutic option to fight infectious diseases, says GlobalData. The leading data and analytics company expects that, while the current market is focusing on gastrointestinal infections, this pathway will soon be used to take on multiple diseases, ranging from cancer to psychiatric disorders, and even COVID-19.

Nancy Jaser, PharmD/MBA, Pharma Analyst at GlobalData, explains: “The gut microbiome is a community of microorganisms found living together in the gastrointestinal (GI) tract. You may have heard some of these referenced as ‘good bacteria’, a phrase used by various probiotic drinks companies. Fascinatingly, scientists are discovering that these bacteria actually play an essential part in the health of many organ systems. Much of the development we are currently seeing in this space is around gastrointestinal infections, leaving huge potential to unlock here in other indications.”

GlobalData’s latest report, ‘Microbiome-Targeting Therapeutics in Infectious Diseases – Thematic Research’, reveals that almost half (10 out of 23*) of gut microbiome-targeting drugs are currently under investigation for treating Clostridioides difficile infections (CDIs), a serious bacterial infection of the large intestine.

Jaser comments: “Interest has sparked across the microbiome-targeting drug space as more experts are becoming aware of its clinical relevance for treating infectious diseases. While non-GI indications are being investigated, CDIs account for a significant chunk (43%) of the current pipeline. Non-GI indications remain largely unexplored when it comes to the gut microbiome, leaving ample opportunities for companies to invest in this novel space.”

While CDI is attracting the most attention, trials are also ongoing for COVID-19, urinary tract infections (UTIs), necrotizing enterocolitis (NEC), and other infectious diseases.

Jaser continues: “Research on the respiratory microbiome has started to attract the attention of more drug developers with the emergence of the COVID-19 pandemic. In the respiratory tract, COVID-19 binds to angiotensin-converting enzyme 2 (ACE-2) receptors on the lungs. Importantly, ACE-2 receptors are also highly expressed on the surface of cells in the stomach, intestines, and rectum. This may explain why many COVID-19 patients develop GI symptoms, which often present before any respiratory symptoms. Viral shedding of COVID-19 has also been found to persist much longer in stool samples than in respiratory swabs, indicating that COVID-19 infection may alter the gut microbiome and play a role in long COVID-19.

“Researchers are currently studying this by comparing a patient’s gut bacteria when they first get a COVID-19 infection to which bacteria are present months later, after long COVID-19 is suspected. While this data is still in early stages, it may reveal the link between the gut microbiome and COVID-19 symptoms, while also identifying potential microbiome targets for treating both COVID-19 and long COVID.”

GlobalData has found that there has yet to be any microbiome-targeting therapies to receive regulatory approval in the 7MM*. One challenge is that it is such a new area. For example, Fecal microbiota transplants (FMT)—whereby stool from a healthy donor is transferred to the gastrointestinal tract of a patient—are currently being used to treat recurrent CDI, but the procedure is not technically approved for clinical use. Instead, the Food and Drug Administration (FDA) and the European Pharmacopoeia (Ph. Eur.) have classified FMTs under the regulatory category of ‘live biotherapeutic products’ (LBPs), which are regulated as biological products.

Jaser adds: “There is no specific guidance on how to submit a New Drug Application (NDA) or apply for marketing authorization for LBPs at this time, but this will likely change as newer innovative therapies continue to emerge and complete late-stage clinical trials.”

GlobalData’s report highlights some of the current gut microbiome-targeting drugs. Rebiotix Inc’s RBX-2660 is the first to enter pre-registration phase in the infectious diseases space and is seeking approval in two indications: CDI and diarrhea. This drug has been granted fast track, orphan drug, and breakthrough therapy designations by the FDA and is also in earlier stage clinical development for UTIs and vancomycin-resistant Enterococcus infections (VRE).

Jaser comments: “If approved, RBX-2660 will gain a first-mover advantage, as the first ‘enema LBP’ to reach the market. However, it will likely face high competition when more convenient ‘oral LBP’ drugs such as Finch Therapeutics’ CP-101 and Seres Therapeutics’ SER-109 enter the market. Both drugs are currently in Phase III trials.”

One of the strongest players in this space, Rebiotix also has a Phase III ‘oral LBP’ drug in development, RBX-7455, which may enter the market around the same time as other Phase III competitors.

Jaser continues: “If both of Rebiotix’s drugs are approved, they will likely capture a high percentage of market share in CDI, as they can target both patient populations that are unable to take oral capsules and patients that have contraindications to using enema products.”

Other novel pipeline drugs in late-stage Phase III development include Evelo Bioscience’s EDP-1815 for COVID-19, Nexbiome Therapeutics’ BGA-1901 for H. pylori infections, Osel Inc’s LACTIN-V for UTIs, and Infant Bacterial Therapeutics’ IBP-9414 for NEC, which has been granted orphan drug and rare pediatric disease designations by the FDA.

* Across the seven major markets (7MM). 7MM = US, Japan, and 5EU (France, Germany, Italy, Spain, and the UK)