One year into clinical hold, FDA has more questions about 'pooled' microbiome therapy
The FDA is still wary about a trial testing a microbiome therapy in patients with steroid-resistant acute graft-versus-host disease (aGVHD).
A year after MaaT Pharma’s IND application in the US was first met with a clinical hold, the French biotech said the agency is maintaining the hold. The crux of the matter, MaaT suggested, has to do with the way it puts together its drug candidate, which is administered as an enema (i.e. an injection of fluid into the bowel).
The Agency acknowledged that it received satisfactory answers from the Company on multiple clinical and manufacturing-related questions that the Agency had initially raised. However, the Agency requires additional information, notably regarding the safety and efficacy of the Company’s “pooling” approach (i.e. mixing donations from multiple donors to achieve higher richness, diversity and better standardization of the product). The Company is also evaluating additional recommendations made by the Agency regarding the trial design.
MaaT began the Phase III open-label trial in Europe in March, following a Phase II European study and an early access program in France. According to Hervé Affagard, co-founder and CEO, more than 120 patients have been treated so far and data to date indicate that the therapy is safe and has promising efficacy.
Backed by several microbiome-focused investors and European funds, MaaT set out to tap into burgeoning research on the relationship between the gut microbiome and the immune system in the development of new treatments for cancer and GVHD. By utilizing rigorous testing standards and manufacturing processes on donor stool, it promised to deliver off-the-shelf “microbiome ecosystem therapies” that can go much further than traditional fecal microbiota transplants, which have long been used to treat C. diff infections under a regulatory grey area.
Still, safety concerns about tainted stool donation and questions on drug quality apparently remain top of mind as regulators review any treatment involving the use of fecal matter, as fellow microbiome player Finch saw firsthand with a clinical hold on its oral drug candidate (the hold has since been lifted).
While it continues to engage with the FDA, MaaT added that it will expand trial recruitment in Europe, applying to open up sites in more countries. It’s also looking to start a Phase II/III trial for a second candidate targeting patients with blood cancers receiving allogeneic hematopoietic stem cell transplantation.