In this guest commentary, Jessica Allegretti, MD, MPH, of the Brigham and Women’s Hospital Crohn’s and Colitis Center, discusses the recent FDA hearing on the agency’s policy of enforcement discretion of fecal microbiota transplantation for recurrent Clostridioides difficile infection.
Monday in Washington, D.C., I attended a hearing called for by the FDA to discuss the issues surrounding their current policy of enforcement discretion regarding FMT. They had speakers from various subsets – mainly industry collaborators, academic and clinician collaborators, and patients and patient advocacy stakeholders – present 10-minute pieces on their thoughts and data surrounding FMT in its current state.
The impetus for a hearing like this from the FDA is because FMT is currently regulated under a policy called enforcement discretion. That means FMT is still deemed experimental and does not have FDA approval. However, the FDA allows us to provide this procedure under this policy of enforcement discretion to patients with recurrent or refractory Clostridioides difficile infection under the stipulations that we explain to patients that it is experimental and go through a rigorous informed consent process.
This hearing made it clear there are two very distinct sides on this issue. On one side is a select group of pharmaceutical or microbiota therapy companies that are developing FMT or FMT-like products. This group argues that the policy of enforcement discretion is unfair because it allows FMT to be conducted in this open label fashion, ultimately hurting enrollment in their clinical trials. A few of these companies have essentially joined together to create a working group that feels strongly that the policy of enforcement discretion should end.
On the other side, there was a very strong argument from clinicians, academic investigators, and patients and patient advocates that enforcement discretion has really enabled access to this life saving therapy. If this option were to go away, there would be many patients who would be left without access to a therapy that is truly considered standard of care at this point.
However, the FDA is still rightfully concerned about the need to collect good, long-term safety data. That falls on us as clinicians and investigators to collect the necessary long-term safety data in a systematic way. The AGA has worked hard to start a national registry to collect these data, and that effort is already under way.
During the open comment section of the hearing, I implored the FDA not to rescind enforcement discretion. Even if a therapy was to become approved and gain licensure, I believe enforcement discretion should only be withdrawn if done very slowly. Even with an approved drug, access may still be very limited.
I sincerely hope that many or all of these companies that have therapeutics in the pipeline gain approval, and I hope their drugs prove to be efficacious and safe, giving us a myriad of choices to offer our patients. That said, I strongly believe there will always be a role for FMT in its current state, especially for our severe, fulminant or ICU-level patients with C. diff. Having the traditional method as an option needs to be a possibility.
Enforcement discretion gives us room for improved access. I do not think it has to be one or none. I offer FMT to my patients, but I also enroll in clinical trials. I have a good, informed discussion, a shared decision-making process with my patients. I let them choose what makes the most sense for them, and I still have many patients who choose clinical trial options. Enrollment in clinical trials is always difficult but not impossible. Our group recently published a study that found that only 25% of patients referred for FMT will even qualify for these trials, highlighting the ongoing importance of FMT provided under enforcement discretion.
From my perspective as a clinician-investigator, I feel strongly that enforcement discretion should not be rescinded. It has expanded access to a life-saving therapy, and I am hopeful that we can work together with industry partners to ensure that access continues. Enrollment in clinical trials should always be an option, not something patients are forced into due to lack of options.
Disclosures: Allegretti reports consulting for Finch Therapeutics and serving as an unpaid scientific advisor for OpenBiome.