Microbiome-based therapies are a promising area in precision medicine, aiming to tailor treatments based on individual microbial compositions. These therapies leverage the unique characteristics of an individual's microbiome—the community of microorganisms living in and on our bodies—to develop personalized medical treatments. This blog aims at providing an overview on how microbiome-based therapies are used in precision medicine.
Treatment Modalities of Microbiome Based Therapies
Probiotics: Live beneficial bacteria that confer health benefits by modulating the host’s microbiome.
Prebiotics: Non-digestible food ingredients that stimulate the growth and activity of beneficial bacteria.
Fecal Microbiota Transplantation (FMT): Transfer of stool from a healthy donor to a patient to restore healthy microbial diversity.
Phage Therapy: Use of bacteriophages to target specific pathogenic bacteria in the microbiome.
Engineered Microbiota: Genetically modified microbes designed to perform specific therapeutic functions.
First US FDA Approved Microbiota Product
The first oral fecal microbiota product, Vowst, was approved by the US Food and Drug Administration (US FDA) in April 2023. Vowst is approved for the prevention of recurrence of Clostridioides difficile infection (CDI) following antimicrobial treatment for recurrent Clostridium difficile infection (rCDI) in people 18 years of age and older. Vowst was granted approval under Priority Review, Orphan and Breakthrough Therapy Designation
Regulation of Microbiome Based Therapies
The regulatory aspects of microbiome-based therapies are complex and evolving. As these therapies represent a relatively new field, regulatory frameworks are still being developed and refined. Here are some key regulatory considerations for microbiome-based therapies:
Classification and Definition: The microbiome-based therapies can be considered biologics, drugs, medical devices, or combination products, depending on their nature and mechanism of action. FMT is often treated as a biological product, but regulations vary by region. In the U.S., the FDA currently exercises enforcement discretion, allowing FMT for certain indications (like Clostridium difficile infection) under specific conditions.
Safety and Efficacy
Clinical Trials: Like all new therapies, microbiome-based treatments must undergo rigorous clinical trials to demonstrate safety and efficacy. This includes preclinical studies, phase I (safety), phase II (efficacy and dosing), phase III (confirmation of efficacy and monitoring of adverse reactions), and phase IV (post-marketing surveillance).
Risk Assessment: Evaluating the risk of infections, adverse immune reactions, and potential long-term effects is crucial, especially for live microbial products.
Manufacturing and Quality Control
Good Manufacturing Practices (GMP): Production of microbiome-based therapies must adhere to GMP to ensure consistent quality, purity, and potency.
Standardization: Developing standardized protocols for the collection, processing, and storage of microbiome samples is essential to maintain product consistency and safety.
US Food and Drug Administration (US FDA) Regulation of Microbiome Therapies
Investigational New Drug (IND) Applications: Microbiome-based therapies typically require an IND application to conduct clinical trials. The FDA reviews preclinical data, manufacturing information, and clinical protocols to ensure the safety of study participants.
Biologics License Application (BLA): For therapies classified as biological products, a BLA must be submitted for FDA approval. This includes extensive data on safety, efficacy, and manufacturing processes.
Fecal Microbiota Transplantation (FMT): Enforcement Discretion: The FDA currently exercises enforcement discretion for FMT used to treat Clostridium difficile infection not responsive to standard therapies. This allows clinicians to use FMT under certain conditions without full regulatory approval.
Investigational Use: For other indications, FMT requires an IND application.
European Medicines Agency (EMA) Regulation of Microbiome Therapies in Europe
Many microbiome-based therapies are classified as Advanced Therapy Medicinal Products (ATMPs) , which include gene therapy, somatic cell therapy, and tissue-engineered products. These products follow specific regulatory pathways tailored to their complex nature. Similar to the FDA’s IND, a Clinical Trial Authorization (CTA) is required to conduct clinical trials in the EU. This includes a thorough review of preclinical and clinical data, as well as manufacturing processes.
International Collaboration: Both the FDA and EMA participate in international efforts to harmonize regulatory standards for microbiome-based therapies. Organizations like the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) play a crucial role in this process.
Market Outlook : Size and Growth of Microbiome Based Therapies
Current Market Size: As of 2023, the global market for microbiome therapeutics was estimated to be around $300 million.
Growth Rate: The market is expected to grow at a compound annual growth rate (CAGR) of over 36.1%, potentially reaching $ 1.7 billion by 2029.
Key Industry Leaders in Microbiome Based Therapies Segment
Seres Therapeutics
Approved Products: Vowst is FDA approved fecal microbiota spores for the treatment of Clostridioides difficile infection.
Product Pipeline:
SER-155: An oral, rationally designed, fermented microbiome therapeutic aimed at gastrointestinal infections, bacteremia, and graft versus host disease (GvHD) in immunocompromised patients.
SER-287 and SER-301: Targeting ulcerative colitis, this product is in Phase 1 and Phase 2 clinical trials to evaluate its efficacy in inducing remission and reducing inflammation.
Vedanta Biosciences
VE303: A consortium of live bacteria designed to prevent Clostridioides difficile infection is entering Phase 3 clinical trials.
VE202: Targeting inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, this product is being tested for its ability to modulate the immune response and restore gut health.
VE707: A microbiota based therapeutic for the treatment of gram-negative infection.
VE818: A microbiota-based therapy for environmental enteric dysfunction which is a third party led trials.
Finch Therapeutics
CP101: Designed to treat recurrent CDI, this oral capsule has shown positive results in clinical trials.
FIN-211: Targeting autism spectrum disorder with gastrointestinal symptoms, this therapy aims to modify the gut microbiome to improve behavior and GI function.
Rebiotix (a Ferring Pharmaceuticals company)
RBX2660: An enema-based microbiota suspension targeting recurrent CDI. It has received Breakthrough Therapy designation from the FDA and is in advanced clinical trials.
RBX7455: An oral formulation for CDI prevention, currently in clinical development.
4D Pharma
Blautix: Designed to treat irritable bowel syndrome (IBS), this therapy aims to improve gut microbiome composition and alleviate symptoms.
Enterome
EO2401: A cancer immunotherapy targeting solid tumors, utilizing microbiome-derived antigens to stimulate an immune response.
EB8018 (TAK-018): Developed in partnership with Takeda, this oral small molecule targets Crohn’s disease by modulating the gut microbiome.
Synlogic
SYNB1618: Targeting phenylketonuria (PKU), this engineered probiotic aims to break down phenylalanine in the gut.
SYNB1891: An engineered biotic for cancer immunotherapy, designed to activate the immune system to target tumors.
Major Investments in Microbiome Therapeutic Startups
After COVID-19, there have been significant investments in microbiome-based therapies, highlighting the growing interest and potential in this field. Some of the
Microbiotica has secured £50 million ($67 million) to advance its pipeline of microbiome-based therapeutics led by British Patient Capital, Cambridge Innovation Capital, and Flerie Invest, among others. Microbiotica focuses on immuno-oncology and inflammatory bowel disease (IBD).
Exeliom Biosciences raised $26 million in a Series A funding round led by CE Ventures, with participation from Biocodex and other venture capital firms. This funding will support their development of microbiome therapeutics.
In 2023, Alba Health secured $2 million in a pre-seed fundraising round headed by Voima Ventures. To date, Alba Health has raised $2.5 million.
Pendulum Therapeutics has raised $111m in funding, and in June 2023, the startup raised $10m from New Zealand-based dairy company Fonterra.
Bac3Gel has raised $1.7m in total funding. The major investors in the company are EIT Health, a European healthcare-focused accelerator and the European Innovation Council through its investment fund EIC Fund.
In 2023, BioMed Technology Holdings raised $2m in a seed round from Alibaba’s Hong Kong Entrepreneurs Fund, Gobi Partners, and The International Medical Co.
In 2022, the BoobyBiome raised $1.6m in pre-seed round with investors Innovate UK, Biomedical Catalyst and biotechnology company aTen Therapeutics. The company has raised $2m in total funding.
Digbi Health raised $5.4m in a series A round led by Accel with Seraph Venture, Ocean Azul Partners and Wisdom in 2021. The company has raised $8.5m in funding.
LyteGro has raised $2.2m in funding. Prominent investors being Innovate UK, angel investors, and Paul Finch.
Pluton Biosciences has raised a total funding of $24.2m. In May 2023, the company raised $16.5m in a series A round led by Illumina Ventures and other investors are RA Capital, Fall Line Capital and First In Ventures.
VeMico has raised a total funding of $33.3m. The Investors are SOSV and accelerator programme RebelBio.
These investments highlight the potential of microbiome-based therapies to address unmet medical needs and the growing confidence in their commercial viability. The combination of strategic partnerships, significant funding, and regulatory milestones is driving the field forward, promising innovative treatments for a range of diseases.
Regulatory compliance, documentation, obtaining approvals, and drug discovery are interconnected processes that must work seamlessly together. Innovative technologies demand skilled regulatory professionals to ensure a smooth journey. Explore the advanced solutions and unparalleled expertise that Artixio offers. We are your trusted partner for all regulatory needs, driving progress and innovation. Contact Artixio at info@artixio.com today.
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