Microbiome Therapeutics Innovation Group Statement on the First and Only FDA-Approved Orally Administered Microbiota-Based Therapeutic
The Microbiome Therapeutics Innovation Group (MTIG) congratulates its member company Seres Therapeutics, Inc. (Nasdaq: MCRB) and Nestlé Health Science on the approval of VOWSTTM, formerly called SER-109, by the U.S. Food and Drug Administration (FDA). This approval marks another historic moment for the microbiome industry as the first FDA-approved orally administered microbiota-based therapeutic with the opportunity to address the prevention of recurrence of C. difficile infection in adults with rCDI, including first recurrence, following antibacterial treatment.
Recurrent C. difficile is a debilitating, and in some cases life-threatening, infection caused by dysbiosis of the gut microbiome that can have a significant impact on a patient’s quality of life and healthcare costs. VOWST harnesses the power of the human microbiome to provide a much-needed oral treatment option for patients suffering with this disease.
“We’d like to congratulate our colleagues at Seres,” said Nikole Kimes, CEO of Siolta Therapeutics and Chairman of MTIG. “The approval of VOWST addresses a critical need for rCDI patients and provides further validation of the microbiome industry.”
MTIG is committed working with stakeholders who share in our mission and seek to collaborate with patients, patient advocates, professional societies/organizations/public health officials, scientists, government policymakers, healthcare providers and payers who seek tangible policy
and regulatory solutions to issues in the emerging microbiome arena.
MTIG Statement on Future of Fecal Transplant Therapy and the Microbiome Industry
The Microbiome Therapeutics Innovation Group (MTIG) notes the importance of the FDA’s finalization of previous guidance to enforce investigational new drug (IND) requirements to the use of FMT to treat CDI not responding to standard therapies. “Patients benefit from products with FDA-approved safety, efficacy, manufacturing controls, and rigorous post-marketing surveillance to ensure long-term safety,” said Nikole Kimes, Ph.D., CEO of Siolta Therapeutics and Chair of MTIG.
Since its founding in 2017, MTIG has worked with stakeholders to recognize the microbiome as one of the new frontiers of medical innovation that has the potential to benefit millions of patients suffering from numerous diseases and reduce significant healthcare costs. MTIG fully supports the continued vigilance of the FDA in regulating this field to better assure that patients have access to safe and effective treatments.
Looking forward, MTIG is committed to continuing its work with FDA to develop guidelines for the application of pharmaceutical development criteria related to microbiota-based therapeutics and for the evaluation of safety parameters related to microbiota-based therapeutic products. As we approach an active 2023 across the industry, we look forward to additional milestones from our MTIG companies including the potential approval of the first-ever oral microbiome therapeutic as Seres Therapeutics approaches its PDUFA mid-April 2023 and additional activities from our therapeutic, diagnostic, and profiling technology companies.
Microbiome Therapeutics Innovation Group Statement on Impact of First-Ever Microbiota Product Approval
The Microbiome Therapeutics Innovation Group (MTIG) once again congratulates its member company Rebiotix, A Ferring Company, on the U.S. Food and Drug Administration (FDA) approval of REBYOTA™, a novel first-in-class microbiota-based live biotherapeutic indicated for the prevention of recurrence of Clostridioides difficile infection (CDI). This news marks a historic moment for the microbiome industry.
MTIG was founded to help recognize the human microbiome as one of the new frontiers of medical innovation. One of those areas is revolutionizing the treatment of challenging gastrointestinal diseases by harnessing the power of the human microbiome. Rebyota has demonstrated the safety and efficacy to improve the quality of life for thousands of patients.
“We congratulate our colleagues at Rebiotix and Ferring,” said Nikole Kimes, CEO of Siolta Therapeutics and Chair of MTIG. “The approval of REBYOTA provides patients with a new and significant treatment option to prevent recurrent C difficile infection.”
MTIG is committed to continuing work with stakeholders who share in our mission and seek to collaborate with patients, patient advocates, professional societies/organizations/public health officials, scientists, government policymakers, healthcare providers and payers who seek tangible policy and regulatory solutions to issues in the emerging microbiome arena.
Microbiome Therapeutics Innovation Group Statement on Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms
On March 12, 2020, the U.S. Food and Drug Administration (FDA) issued a safety alert regarding the use of fecal microbiota for transplantation (FMT) due to infections caused by enteropathogenic Escherichia coli (EPEC) and Shigatoxin-producing Escherichia coli (STEC).
The FDA safety alert states six patients who received FMT products from a stool bank company for treatment of Clostridium difficile developed infections caused by EPEC or STEC.
Our membership supports the development of therapeutic microbiota-based products that are safe and effective. Our coalition companies are adhering to FDA guidelines for Investigational New Drugs, which include donor screening/testing and/or quality control requirements. MTIG supports the FDA Investigational New Drug regulations for patient access to safe and effective treatments. We look forward to further discussions with the FDA to develop guidelines for the application of pharmaceutical development criteria related to microbiota-based therapeutics and for the evaluation of safety parameters related to microbiota-based therapeutic products.
Microbiome Therapeutics Innovation Group Statement on FDA Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Risk of Serious Adverse Reactions Due to Transmission of Multi-Drug Resistant Organisms
On June 13, 2019, the U.S. Food and Drug Administration (FDA) issued a safety alert regarding the use of fecal microbiota for transplantation, or FMT:
Our MTIG members are committed to the development of therapeutic microbiota-based products that are safe and effective. All of our member companies are developing investigational products in compliance with the FDA guidelines for Investigational New Drugs, including donor testing and/or quality control requirements. We are working actively with the FDA to develop guidelines for the application of pharmaceutical development criteria related to microbiota-based therapeutics and for the evaluation of safety parameters related to microbiota-based therapeutic products. MTIG fully supports the continued vigilance of the FDA in regulating this field to better assure that patients have access to safe and effective treatments.
Microbiome Therapeutics Innovation Group Position Statement on FMT
The microbiome is essential to human health providing resistance to infectious diseases, regulating the immune system, and impacting metabolism and digestion.1 Through a complex and vast network of interacting microbes, the microbiome engages both directly and indirectly with the host to affect neurologic, physiologic and immunologic functions.2 Disruption of this complex ecosystem is now associated with a multitude of chronic and infectious diseases.
Groundbreaking drug products that modulate the microbiome have the potential to address a wide spectrum of health challenges. The role of the microbiome is best understood in recurrent Clostridium difficile (C. diff.) infection, but additional clinical research is studying the microbiome’s role in other disease states including, for example, inflammatory bowel disease (IBD),3 irritable bowel syndrome (IBS), liver disease,4 colon cancer,5 neurological disorders,6 and outcomes of cancer immunotherapies7.
The foundational importance of the microbiome to these diseases and the curative potential of microbiome modulation began with research into fecal microbiota transplantation (FMT). FMT is an investigational procedure that historically consisted of a physician collecting stool from a healthy individual and subsequently administering it to a patient. At present, FMT is most commonly administered for the treatment of C. diff. infection in patients who fail other treatment options. Although published data suggests that FMT can be an effective therapy to manage recurrent C. diff. infection,8 the safety and efficacy of FMT have not been fully demonstrated in randomized double-blind controlled clinical trials or evaluated by the Food and Drug Administration (FDA).9
FDA has determined that FMT administered to treat C. diff. infections meets the definitions of a biological product and a drug and is therefore subject to premarket review and approval under the Public Health Service Act (“PHS Act”) and the Federal Food, Drug, and Cosmetic Act (“FDCA”).10 Under this determination, clinical trials to demonstrate safety and efficacy are required for FDA approval and commercial distribution of FMT as set forth in the Investigational New Drug (“IND”) regulations, 21 CFR Part 312. In 2013, FDA took the position that FMT may be used as an investigational therapy to treat C. diff. infections not responding to standard therapies, provided the physician obtains adequate informed consent from the patient, including acknowledgement of the investigational nature and risks of FMT.11
In March 2016, FDA issued a Draft Guidance proposing to narrow the IND exemption to the use of FMT to treat C. diff. infections not responding to standard therapies, provided that:
- the treating physician obtains informed consent, including a discussion of FMT’s “reasonably foreseeable risks”;12
- the FMT product is not obtained from a stool bank; and
- the stool donor and stool are “qualified by screening and testing” under a physician’s supervision in providing the FMT product to treat a patient.13
The FDA’s decision not to enforce IND requirements under these narrow conditions has created an unintended situation whereby stool bank companies screen donors, process samples, and commercially distribute FMT treatments without complying with IND requirements and without establishing the safety and efficacy of their drug products through prospective clinical trials. At present, this 2016 Draft Guidance has not been finalized.
Patients benefit from products with FDA-approved safety, efficacy, manufacturing controls, and rigorous post-marketing surveillance to ensure long-term safety. FDA approval would also broaden access to a larger patient population through enabling coverage by Medicare and private insurance companies, as well as providing physicians a less burdensome process for administering treatment. At present, the development of approved therapies is facing substantial delays despite extensive outreach, education and recruitment efforts, largely due to stymied enrollment in clinical trials because of the broad distribution of unapproved FMT.
MTIG Position Statement on FMT
The Microbiome Therapeutics Innovation Group (MTIG) is a coalition of companies leading the research and development of FDA-approved microbiome therapeutic drugs and microbiome-based products to address unmet medical needs, improve clinical outcomes, and reduce health care costs.
- MTIG agrees with FDA that patients should access FMT treatment through clinical trials and supports continuing patient access to physician-prepared FMT with donor controls and informed consent, consistent with the FDA’s Draft Guidance. MTIG also strongly supports FDA’s position, as stated in the Draft Guidance, that enforcement discretion should not extend to unregulated commercial-scale FMT stool banks that have not established safety and efficacy through FDA-regulated clinical trials.
- MTIG supports consistent and equitable FDA oversight and regulation to ensure that commercial-scale FMT products implement and adhere to the rigorous clinical, regulatory manufacturing and quality controls to which other microbiota drug products adhere.
- Consistent with years of Agency practice and precedent, MTIG concurs with FDA’s regulatory classification of FMT as a drug product that is subject to IND requirements that protect patient safety and assure clinical experiments are conducted in accordance with the law.
- MTIG supports companies in their pursuit of regulatory approvals for microbiome therapeutics and microbiome-based products.
- Streamlining FDA regulatory procedures to increase clarity and decrease development time is the best way to assure that safe and effective microbiome therapeutics reach patients and providers. MTIG encourages the FDA to issue guidance for microbiome therapeutics development topics, such as clinical trial designs, endpoint and biomarker selection, use of expedited review pathways, and product nomenclature.
1 de Vos, WM, de Vos, EAJ. Role of the intestinal microbiome in health and disease: from correlation to causation, Nutrition Reviews. 2012;70(Suppl. 1):545-56.
2 Gupta, S, Allen-Vercoe, E, Petrof, E. Fecal Microbiota Transplantation: In Perspective, Therapy Adv. Gastroentology. 2016 Mar;9(2):229-39.
3 Halfvarson, J., et al., Dynamics of the human gut microbiome in inflammatory bowel disease, Nat. Microbiol. 2017 Feb;DOI:10.1038/nmicrobiol.2017.4.
4 Adolph, TE, et al., Liver-Microbiome Axis in Health and Disease, Trends Immunol. 2018 Sep;39(9):712-23.
5 Miyake, Y, Yamamoto, K. Role of Gut Microbiota in Liver Diseases, Hepatol. Res. 2013 Feb;43(2):139-46.
6 Mayer EA, et al., Gut Microbes and the Brain: Paradigm Shift in Neuroscience, J. Neurosci. 2014 Nov;34(46):15490-496.
7 Elkrief, A, et al., The intimate relationship between gut microbiota and cancer immunotherapy, Gut Microbes. 2018 Oct;DOI:10.1020/19490976.2018.1527167.
8 FDA Draft Guidance for Industry, Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies, (hereinafter, Draft Guidance), at *2, available at https://www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/vaccines/ucm488223.pdf (March 2016).
9 Draft Guidance, at *2.
10 Draft Guidance, at *1.
11 FDA Guidance for Industry, Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies, (hereinafter, Guidance), at *1, available at https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/UCM361393.pdf (July 2013).
12 Draft Guidance, at *3.
13 Id. at *4.