How to overcome barriers in the adoption of microbiome-based therapies

Growing evidence indicates that imbalances in bacteria living in the human microbiome (dysbiosis) can lead to a range of diseases that can potentially be treated by restoring harmonious bacterial populations (symbiosis).¹ This connection between the microbiome and human health shows the potential of the microbiome as a prime therapeutic target and has inspired the development of several microbiome-based therapies that are currently progressing through pre-clinical and clinical trials.² Of these, probiotic therapies – which administer live microbes into patients to restore bacterial symbiosis³ – are the most advanced. With several probiotic therapies progressing towards commercialisation, the high growth potential of the microbiome therapeutics market is clear.

There are several barriers hindering the development and commercialisation of microbiome-based therapies and the willingness of other companies to enter the sector, including:

1. the inability to clearly demonstrate the clinical applications of these therapies;
2. unclear guidelines for their use in physicians’ treatment algorithms; and
3. the nascency of the field and its largely uncharacterised nature.^4,5

Currently, there is only one marketed microbiome-targeted therapy – faecal microbiota transplantation (FMT), which is widely used in clinical practice to treat recurring Clostridioides difficile infections (rCDI). FMT involves extracting healthy bacteria from another individual’s faecal matter and transferring it directly into the infected patient.⁶ As the microbiome is directly related to the etiology of rCDI, FMT has been accepted at many medical centres, despite its lack of formal US Food and Drug Administration (FDA) approval, as the most effective treatment for patients with rCDI. However, FMT has occasionally been shown to negatively interact with a patient’s existing microbiome, inadvertently introducing disease-causing bacteria.^7,8

As several promising probiotic therapies advance through clinical trials, drug manufacturers seek to learn from the shortcomings of FMT and address stakeholder concerns and other challenges in their efforts to provide improved microbiome-based treatment options for rCDI and other indications (see Figure 1).

Figure 1: Clinical timeline of leading microbiome-based therapies – January 2021
rCDI: Recurrent C. diff Infection, UC: Ulcerative Colitis, IBD: Inflammatory Bowel Disease, MM: Metastatic Melanoma [Source: CRA-Conducted Analysis (2021)].

Hurdles in research, development and potential launch

To successfully drive development and eventual adoption of microbiome-based therapies, including those advancing toward regulatory approval, drug manufacturers must address three key barriers. These revolve around convincing stakeholders, from patients to healthcare providers to payers, of the value of microbiome therapeutics in improving patient outcomes:

• Lack of robust efficacy and safety data: Drug developers must convince physicians of the real-world value microbiome-based therapies provide based on limited clinical data. Some physicians are calling for more robust clinical data validating the effectiveness of these emerging therapies and highlight the lack of consensus around how manipulating the microbiome ultimately impacts human health.⁹ While some healthcare providers agree that the microbiome has significant influence on disease pathology and that microbiome manipulation will be critical in addressing a range of diseases including neurodegenerative, inflammatory and metabolic diseases, others believe microbiome-based therapies should not be incorporated in treatment decisions due to the lack of empirical evidence supporting therapeutic use.¹⁰
• Undefined commercial opportunity: It is unclear exactly how physicians will adopt microbiome-based therapies into clinical practice, as clinical trials often show that these products can be used to address a range of unmet needs. This can present significant risk for manufacturers, especially those developing first-to-market therapies for which there is no precedent for clinical development, regulatory reviews or launch and marketing strategies. Manufacturers will need to identify the area of highest commercial opportunity in this untapped market and collect supporting market data to showcase to potential customers.
• Limited awareness among potential customers: Given the nascency of the microbiome sector, many patients and physicians have a limited understanding and awareness of microbiome-based therapies and their unique approach to treating diseases. They also often do not understand what factors differentiate these types of therapies from one another. Once a therapy is approved, it will be critical to effectively communicate a value proposition that resonates with target customers and that aligns with their needs to support adoption.

Strategies to encourage broad adoption

As shown in Figure 2, the key to successfully driving adoption of approved microbiome-based therapies is to overcome the barriers outlined above and shape current stakeholder opinions by convincing them of the value of these therapies.

Figure 2: Highlighted opportunities to overcome barriers in developing microbiome-based therapeutics [Source: CRA-Conducted Analysis (2021)].

A first step in this effort is to gain an in-depth understanding of the commercial potential of a product and identify the use that offers the highest commercial potential. This will require the development and application of an opportunity assessment framework, which should encompass specific metrics for assessing a range of factors including 1) the strength of a product’s value proposition, 2) its ability to be put into clinical practice, 3) the size of the addressable patient population based on target intervention points in the patient journey, 4) likelihood of physician and patient adoption, 5) level of competition and 6) likelihood of reimbursement by payers.

Developing the value proposition

Once manufacturers identify the opportunity with the highest commercial potential, they must take steps to reaffirm the value proposition of their product to ensure it aligns with the unmet needs of target customers, can be sufficiently supported by generated data and resonates with all stakeholder audiences (eg, physicians, patients and payers).

Education and competitive positioning

Manufacturers will also need to build broader awareness of the microbiome and its potential role in causing different diseases, as well as how therapies targeting the microbiome work and their proven clinical benefits. This might involve execution of educational campaigns and physician training, as well as the development of educational resources and support materials. Increased education and awareness efforts about a specific therapy can also help differentiate it from existing standard-of-care treatments and future market entrants. It is essential that manufacturers think strategically about positioning their therapy versus the competition to demonstrate its unique value proposition and support uptake post-launch.

Generating clinical data

Perhaps the most important step on the road to potential approval and adoption of microbiome-based therapies is developing a comprehensive strategy for effectively generating the level of clinical data required by regulators and preferred by target customers. This evidence generation plan must detail how manufacturers will identify critical data gaps relevant to a product’s value proposition (eg, patient outcomes, health economic and outcomes research data), prioritise these data gaps and generate the required data to substantiate a product’s clinical use, value proposition and positioning. Execution of an effective evidence generation strategy will likely involve a range of activities including retrospective claims analyses, prospective chart studies and additional clinical trials. The most successful manufacturers of microbiome-based therapies will execute these activities in an affordable and expedient manner.

Communicating value

Following the collection of required clinical data, manufacturers must communicate the value proposition of a product with target customers. This might include communicating real-world payer or physician testimonials about a product, training sales teams to address issues or concerns raised by physicians, creating a FAQ resource for potential patients and developing a payer budget impact model. Whatever the strategies, they should be tailored to the product and needs of each customer to ensure efforts are targeted and cost-effective and that the value proposition resonates with target stakeholders.

Conclusion

Co-ordination of successful development and commercialisation for emerging microbiome-based therapies requires strategic execution of these tactics, supported by experts knowledgeable in the field who have experience in clinical development and commercialisation of innovative technologies and understand what it takes to ensure uptake with customers post-launch. A successful launch of probiotic treatments, including potentially curative therapies, will be contingent on establishing a strong value proposition, building robust supporting evidence around this value and positioning versus current and future competition. If these critical drivers are in place, it will help enable novel probiotics to navigate this exciting new field and capitalise on its high growth potential in the years ahead.

References

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3. Vanderhoof, J. (2017, March). 147 Early changes in the human Microbiome alter immune function and immunologically mediated disorders. Journal of Animal Science, 95(2), 69-70.
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6. Group, M. T. (2019). 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. Retrieved from MTIG.
7. Wong, A., & Levy, M. (2019, June). New Approaches to Microbiome-Based Therapies. mSystems.
8. FDA. (2016, March). Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies. Retrieved from Food and Drug Administration.
9. Adolph, T., Grander, C., Moschen, A., & Tilg, H. (2018, May). Liver-microbiome axis in health and disease. Trends Immunology, 39(9), 712-723.
10. Tilg, H., & Moschen, A. (2015, May). Food, immunity, and the microbiome. Gastroenterology, 148(6), 1107-1119.