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FDA advisers back microbiota-based treatment for gut infection

A panel of Food and Drug Administration advisers gave their support to Rebiotix’s microbiota-based treatment for a type of intestinal infection, potentially putting it on track to become the first approved therapy of its kind in the U.S.

Members of the expert committee voted 13-4 that the treatment, called Rebyota, was effective in treating recurrent infections from Clostridioides difficile, or C. diff. The panel concluded its benefits, while modest, are significant enough for a long-suffering patient population with no other approved options when antibiotics fail to work.

The Minnesota-based biotechnology company made its case with six clinical studies, including two Phase 3 studies, that tested at least one dose of Rebyota in 978 patients. An analysis of the Phase 3 results showed Rebyota had a 70.6% success rate in preventing recurrent infection at eight weeks after one dose compared to a 57.5% success rate with placebo, or a 13.1% difference.

Additionally, the panel voted 12-4, with one abstaining, in favor of Rebyota’s safety profile. The advisers who voted “no” cited the higher number of side effects in treated patients compared to placebo.

“Were the harms that occurred to those patients justified by the improvement that the patients received?” asked panelist Jay Portnoy, a medical director at Children’s Mercy Hospital in Missouri who voted against Rebyota on both efficacy and safety. “These patients are desperate to get a treatment … and the last thing I want to do is to subject them to a treatment that’s not effective,” he said.

The FDA isn’t required to follow the panel’s recommendations, but it typically does.

Several panelists were disappointed by the number of participants in the studies. Rebiotix said it found it difficult to recruit patients for its trials, some of whom preferred to turn to the unapproved use of fecal transplants rather than possibly receive a placebo in a clinical study.

The FDA has allowed the investigational use of fecal transplants since 2013 under its enforcement “discretion.” Panelists who spoke in support of Rebyota said it could provide a standardized and approved treatment that the agency would be better able to monitor for effectiveness and safety.

“What’s out there for patients is they can get [a fecal transplant] from their roommate or, if this is available, they can get a defined [fecal transplant] that has undergone some sort of quality control,” said Eric Rubin, an adjunct professor of immunology and infectious diseases at Harvard University who voted in support of the treatment. “I think that if we have that product, it’s going to actually enhance our ability to tell how well it works.”

Rebiotix is one of several companies pursuing microbiota-based medicines to treat C. diff, a drug-resistant bacteria responsible for half a million infections annually. It can cause diarrhea and, in some cases, life-threatening colon inflammation. It caused more than 12,000 deaths in 2017.

Seres Therapeutics is also seeking the agency’s approval for a C. diff treatment. Unlike Rebyota, which is given via enema, Seres’ treatment is taken orally. The company has faced clinical challenges in the past and altered its testing plans after its lead prospect for treating C. diff infections missed in a Phase 2 study in 2016. Seres reported positive results for the treatment in June and completed its application to the FDA earlier this month.

Finch Therapeutics is developing an oral treatment for C. diff, too, but has faced setbacks and this month laid off more than a third of its staff.

All three experimental treatments are derived from donor samples of gut bacteria, an approach that requires testing for drug-resistant organisms and emerging threats like COVID-19 and monkeypox. The FDA has issued four safety warnings related to the investigational use of fecal transplants since 2019.

“We are monitoring for emerging threats and doing surveillance,” said Rebiotix chief operating officer Greg Fluet. The company has a quarantine period for all manufactured product, which is stored frozen for up to three years. “And we saw this in COVID and again with monkeypox, we still had a sufficient inventory product to maintain continuity of supply.”

Rebiotix is owned by Ferring Pharmaceuticals, which bought the company in 2018.