Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved Vowst (fecal microbiota spores, live-brpk), the first ever oral live microbiota therapeutic approved for the prevention of recurrent Clostridioides difficile infections (rCDI) and the second overall approval in what is an emerging class of treatments to stop recurrence of the infectious disease.¹

The treatment, formally called SER-109, developed by Seres Therapeutics, is manufactured through an inactivation of donor vegetative bacteria, parasites, fungi, and viruses using ethanol. After this process, the remaining product contains purified firmicutes spores, which are resistant to gastric acid and allows for oral administration. Vowst is given in 4 capsules on days 1 to 3, after which the spores germinate and replicate in the GI tract.

“Today’s approval provides patients and healthcare providers a new way to help prevent recurrent C. difficile infection,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “The availability of a fecal microbiota product that can be taken orally is a significant step forward in advancing patient care and accessibility for individuals who have experienced this disease that can be potentially life-threatening.”

Reaction

In an interview with HCPLive®, Sahil Khanna, MBBS, MS, Division of Gastroenterology and Hepatology, Mayo Clinic and investigators on recent Vowst trials, said the approval will essentially give patients, clinicians, and payers now an option for treatment for recurrent CDI, a big boost in eliminating recurrence.

“I think we are at a very exciting time for the management of recurrent C difficile infection,” Khanna said. “We now have for the very first time not 1, but 2 microbiome based therapies for management of recurrent C. difficile infection. It’s a huge win for our patients, it’s a huge win for our providers.”

ECOSPOR

The approval is largely based on the results of the ECOSPOR trials, a series of studies testing the new treatment in comparison to placebo for reducing the risk of rCDI. Recently, investigators presented data from the latest iteration of ECOSPOR from the phase 3, single-arm, open label ECOSPOR IV trial, where investigators examined patients at 72 US and Canadian outpatient sites between October 2017 and April 2022. Each patient was an adult with recurrent CDI.²

The participants were divided into 2 cohorts—rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (n = 29) and patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry (n = 234).

The results also show 8.7% (n = 23; 95% confidence intervals [CI], 5.6-12.8%) had recurrent CDI at week 8 (n = 4; 13.8%; 95% CI, 3.9-31.7% in cohort 1 and n = 19; 8.1%; 95% CI, 5.0-12.4% in cohort 2).

This was similar at week 8 (n = 5; 6.5%; 95% CI, 2.1%-14.5%) as in patients with 2 or more recurrences (n = 18; 9.7%; 95% CI, 5.8%-14.9%).

After further analysis of select baseline characteristics, the investigators found low recurrent CDI rates in the cohort of patients aged younger than 65 years, compared to those older than 65 years (n = 5; 4.0%; 95% CI, 1.3%-9.0% vs n = 18; 13.1%; 95% CI, 8.0%-20.0%).

The same was true for patients enrolled on positive PCR results compared to those with positive toxin EIA (n = 3; 4.3%; 95% CI, 0.9%-12.2% vs n = 20; 10.4%; 95% CI, 6.5%-15.6%).

Vowst and RBX2660

In recent years, Vowst and RBX2660 (Rebyota) went neck and neck in competition to be the first live microbiota therapeutic to gain approval by the FDA for rCDI. RBX2660, developed by Ferring Pharmaceuticals and approved on November 30, 2022, is prepared from stool donated by qualified individuals and administered rectally as a single dose. RBX2660 is a standardized, stabilized, investigational microbiota-based live therapeutic.³

In an interview with HCPLive®, Paul Feuerstadt, MD, Assistant Clinical Professor of Medicine, Yale School of Medicine, explained how the 2 treatments are largely different.

“The only real similarity behind these 2 products is that they are donor derived, they come from human stool,” Fuerstadt said. “But the processes behind these 2 products and the data behind these products are remarkably different and the studies that looked at these products are different.”

The main differences are that RBX2660 is a broad consortium of microorganisms that is administered as a single rectal administration with a wash out period. On the other hand, Vowst just focuses on a purified consortium of Firmicutes spores derived from donor stools and administered through an oral capsule.

FMT

Both products have emerged due to the success of success of fecal microbiota transplantation (FMT) as a technique to treat rCDI.⁴

FMT is a relatively new treatment that involves taking feces from healthy donors to rebuild the gut microbiota of a diseased individual. FMT is delivered through upper or lower endoscopy via enemas or capsules.

However, FMT is currently not an FDA approved option and many stakeholders have said in the past it is unlikely the treatment would ever garner FDA approval.

References:

1. Office of the Commissioner. FDA approves first orally administered fecal microbiota product for the prevention of recurrence of Clostridioides difficile infection. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-orally-administered-fecal-microbiota-product-prevention-recurrence-clostridioides. Published April 26, 2023. Accessed April 26, 2023.

2. Walter, K. (2023, February 13). Ser-109 reduces rate of recurrent CDI. HCP Live. Retrieved April 26, 2023, from https://www.hcplive.com/view/ser-109-reduces-rate-recurrent-cdi

3. Walter, K. (2022, December 1). Sahil Khanna, MBBS, MS, reacts to the historic approval of RBX2660 for recurrent CDI. HCP Live. Retrieved April 26, 2023, from https://www.hcplive.com/view/khanna-reacts-historic-approval-rbx2660-recurrent-cdi

4. Walter, K. (2023, February 21). FMT cost-effective compared to antibiotics in recurrent C difficile infection treatment. HCP Live. Retrieved April 26, 2023, from https://www.hcplive.com/view/fmt-cost-effective-antibiotics-recurrent-c-difficile-infection-treatment