Nearly 8 in 10 patients with recurrent C. diff. Infection were successfully treated after up to 2 doses of the microbiota-based therapy.
New phase 2 data suggests a human microbiota-based therapeutic offers not only effective, but also durable, responses in patients with recurrent Clostridioides difficile infection (CDI).
The study, published in BMC Infectious Diseases, suggests many patients will benefit from the therapy, called RBX2660, for at least two years.
If eventually approved by the Food and Drug Administration (FDA), RBX2660 would be a first-in-class product. However, the science behind it, and the idea that the healthy microbiota from donors can be leveraged to help patients struggling with repeat cases of CDI, is one of the most prominent areas of research in the space.
Stuart Johnson, MD, a professor of medicine at Loyola University Medical Center and a physician and scientist at the Hines Department of Veterans Affairs Hospital, near Chicago, said the first iteration of this type of therapy, fecal microbiota transplant (FMT), can be effective, but he added that it also comes with safety concerns, particularly if donor screening protocols are not carefully followed.
The new therapy, which is being developed by Ferring Pharmaceuticals, is a standardized and stabilized live therapeutic. The standardization and stabilization processes help ensure both efficacy and safety, said Johnson, one of the new study’s co-authors.
“It comes from very healthy donors with a very healthy microbiota and they are screened for their symptoms, and screened periodically,” he told Contagion.
The study was based on an evaluation of 142 patients who sought care at one of 29 regional healthcare centers in the United States and Canada. Each of the patients had experienced at least two recurrences of CDI following a primary case and treatment with antibiotics, or had at least two cases of severe CDI that warranted hospitalization. These patients were given up to 2 rectally administered doses of the therapy, 7 days apart. The primary endpoint of the trial was treatment success compared to a historical control group made up of patients treated with standard-of-care therapy for recurrent CDI. In addition, investigators took fecal samples from patients in order to understand changes in patient microbiomes since the intervention.
The data showed that 112 patients (78.9%) were successfully treated, which was defined as the absence of CDI diarrhea and no need for retreatment in the 8 weeks following dosing. In the historical control group of 75 patients, only 23 (30.7%) achieved the same target.
Of 97 patients evaluable at 24 months, the investigators found 88 patients (91%) had no more recurrence of CDI for a full 24 months. Moreover, the fecal analysis suggested that patients who responded to the therapy experienced long-lasting changes to their microbiome, persisting even after two years.
“It's very reassuring that this response went up to 24 months for 91% of the evaluable patients which was also corroborated by the change in the microbiome which lasted as well,” Johnson said. “So I think that that's reassuring that what we think is going on, is going on. It gives me more confidence that this is very effective, and not transient.
The FDA has already granted RBX2660 its Fast Track, Orphan, and Breakthrough Therapy designations.
Johnson, who is both a clinician and a researcher, said he is excited by the therapy and sees the potential for significant changes to day-to-day care of recurrent CDI, if RBX2660 makes it to final approval.
“When this becomes commercially available, it really is going to change my practice,” he said. “I’ll probably use this earlier than that later.”