Microbiome and fecal transplant therapeutics
Life sciences research continues to expand into new domains in the pursuit of innovative therapies. Along with this expansion comes a need for new regulations to ensure efficient and safe use of novel products. In the case of microbiome and fecal transplant therapeutics, the regulatory landscape is still uncertain, creating divergent outlooks for both patients and manufacturers alike. CBPartners has explored the pros and cons of different regulatory approaches, in order to better understand the balance of factors that will determine the future for this exciting area of research.
Current dynamics of human microbiome and fecal transplant treatment
Given the growing awareness of microbiome therapies and the increasing demand for effective therapies in chronic diseases. The outlook for microbiome therapeutics has reached a fever pitch. In 2018, the global human microbiome market potential was estimated to be USD 190 million. With the figure expected to reach USD 620 million by the end of 2024.
The applications of microbiome therapy have been found in various diseases, including Clostridium difficile infection (CDI) and Crohn’s disease, often via fecal microbiota transplantation (FMT). FMT involves the transfer of healthy bacteria through a processed mixture of liquid stool, with the aim to restore the balance of bacteria in the recipient’s intestine.
To illustrate the role of this unusual treatment, let’s take a closer look at the case of CDI. Historically the use of FMT has not been recognized as appropriate by the Food and Drug Administration (FDA). But more recently FMT became an Investigational New Drug (IND) for patients not responding to standard therapies (e.g., antibiotics). Furthermore, to respond to concerns regarding the potential restricted access to FMT, the FDA announced “enforcement discretion” to allow doctors to provide FMT for eligible patients without filing an IND application, provided that the FMT product is not obtained from a stool bank. As the FDA considers the options for regulation of this technique, it’s worth exploring the Price and Market Access (P&MA) implications of the two potential regulatory approaches.
What are the access implications for FMT if FDA decides to regulate it as a drug?
If FMT is to be regulated as a drug, the access implications can be similar to that of antibiotics treatment (e.g., DIFICID™ – fidaxomicin, $MRK). In a nutshell, the regular FDA approval process will apply to FMT, meaning that clinical trial evidence will be mandatory for the New Drug Application. Furthermore, inspection of the manufacturing sites of the FMT products will also be factored into the final FDA decision. After an FDA approval is granted for FMT, the product will be assessed by individual health plans’ Pharmacy and Therapeutics committees to develop coverage guidelines, which depending on the cost could include management controls such as prior authorizations. Patients would also be subject to out-of-pocket cost sharing, a similar process to the payment system in place for prescription drugs.
What are the access implications for FMT if FDA decides to regulate it as a procedure?
If FMT is to be regulated as a procedure, the access environment is likely to remain the same as it currently stands, meaning that eligible patients could access FMT without participating a clinical trial.
What are the pros and cons of being regulated as a drug?
Among competitors that can supply stool samples, the market authorization holder is likely to expect a broader uptake of FMT within the USA. As FDA approvals signal satisfying efficacy and safety data, this should address any concerns regarding the centralized manufacturing in stool banks. Further, a higher price potential is anticipated based on patent protection or first-to-market advantage, with its cost of production potentially to be reduced through the economics of scale.
On the other hand, hurdles to obtain such approval are expected, which could negatively impact patient access should manufacturers decide not to pursue the approval. Firstly, the FDA approval process is characterized with high evidence requirement and lengthy process. The challenge which could be further exacerbated as treatment paradigm (e.g., emergence of FMT-derived therapies, vaccines and targeted antibiotics) evolves, meaning that clinical trial designs need to be carefully articulated to ensure acceptance of the clinical trial by both the FDA and payers. Secondly, safety concerns regarding stool bank, as seen in the recent trial suspension due to patient death from severe infection, indicate the substantial need to ensure that all donated stool is screened for dangerous organisms.
Additionally, FMT would face competition vs. FMT-derived therapies (e.g., oral capsule SER-109), which could potentially offer therapeutic alternatives for patients with CDI not responding to standard therapies. Higher barriers to entry and a higher price potential vs. FMT are expected due to additional patent protection. Although the option to have oral therapies vs. FMT procedures could be positively perceived given the likely higher quality of life and reduced healthcare resource utilization, issues related to comparable efficacy vs. FMT and patient acceptability would need to be explored to compare the access potential of FMT vs. FMT-derived therapies.
Last but not least, there is the issue of “generic” stool substitution. While a firm may conduct a clinical trial and achieve evidence of the benefits for FMT, it would be quite difficult for that firm to prevent physicians from obtaining stool from a stool bank generally and using it for the same disease. Without a mechanism to enforce the patented application of FMT, the investment in demonstrating FMT’s clinical use is significantly reduced.
FMT remains a promising therapy given its potential application to various difficult-to-treat diseases and the likely increase in its uptake as awareness of this treatment rises. If the FDA issues the decision to regulate FMT as a drug, regular evidence requirements would be required; while this would improve understanding of the treatment, clinical trials could be costly and time-consuming.
While patients and physicians may benefit from greater confidence in the treatment, higher prices may accompany drug-like regulation, increasing patient cost sharing and possible barriers to access. As the regulatory environment for this new treatment takes shape, the pharmaceutical industry will be watching closely to understand this developing opportunity.