The recent approval of the first oral fecal-derived microbiota therapy to prevent the recurrence of Clostridioides difficile (C. diff) infection in patients was welcome news for physicians who’ve struggled under the weight of having too few treatment options for the prevention of C. diff recurrence.
The product, developed by Massachusetts-based Seres Therepeutics and marketed as Vowst, was approved by the U.S. Food and Drug Administration on April 26. It is approved for use in adults who have already been treated with antibiotics for a recurrent infection with C. diff bacteria.
and is designed to be delivered in four capsules taken daily for 3 days.
Gastroenterologist Phillip I. Tarr, MD, division chief of gastroenterology at Washington University, St. Louis, and chair of the American Gastroenterological Association Center for Gut Microbiome Research and Education, said that prevention of recurrent C. diff infection “remains challenging,” and that Vowst “provides the first FDA-approved, orally administered microbiome therapeutic with which to achieve this goal. This advance also makes us optimistic we might soon be able to prevent other disorders by managing gut microbial communities.”
Vowst is the second therapy derived from human stool to be approved for the indication in less than 6 months. In December, the FDA approved Rebyota (Ferring), a rectally delivered treatment that also uses microbes from donor feces. Both products were given priority review, orphan drug, and breakthrough therapy designations by the agency.
C. diff infection can be aggravated by an alteration of normal gut flora associated with antibiotics treatment, leading to cycles of repeated infections. Infection can produce diarrhea, abdominal pain, fever, and severe morbidity. In the United States, an estimated 15,000 to 30,000 deaths per year are linked to C. diff. Risk factors for recurrent infection include being 65 or older, hospitalization, being in a nursing home, a weakened immune system, and previous infection with C. diff.
Therapies transplanting fecal microbiota from donors have been used since the 1950s as treatments for recurrent C. diff infection, and in the past decade, as stool banks recruiting screened donors have made fecal microbiota transplants, or FMT, standard of care. However, only in recent years have fecal-derived therapies become subject to standardized safety and efficacy testing.
Both the current FDA-approved products, Rebyota and Vowst, were shown in randomized controlled trials to reduce recurrence of C. diff infection, compared with placebo. In a phase 3 clinical trial of Rebyota (n = 262) in antibiotic-treated patients, one rectally administered dose reduced recurrence of C. diff infection by 70.6% at 8 weeks, compared with 57.5% for placebo. A phase 3 study of Vowst (n = 281) showed recurrence in treated subjects to be 12.4% at 8 weeks, compared with nearly 40% of those receiving placebo (relative risk, 0.32; 95% confidence interval, 0.18-0.58; P less than .001).
Despite screening protocols that have become increasingly homogenized and rigorous, FMT is associated with the risk of introducing pathogens. Vowst is manufactured with purified bacterial spores derived from donor feces, not whole stool. Nonetheless, FDA noted in its statement that Vowst could still potentially introduce infectious agents or allergens.
