As expected, Seres Therapeutics Inc. gained U.S. FDA approval of the BLA for the oral microbiome therapeutic Vowst, formerly known as SER-109, for prevention of recurrent Clostridium difficile infection (rCDI), accepted for priority review in October of 2022 without an advisory committee meeting.

Vowst, granted priority review, breakthrough therapy and orphan designation, is a microbiome therapeutic composed of purified Firmicutes spores. In the U.S., rCDI cases number almost 170,000 each year, making the bug one of the top three most urgent bacterial threats, according to the CDC.

The application for Vowst was supported by the results of a completed phase III program including the Ecospor III and Ecospor IV experiments. Ecospor III, a multicenter, randomized, placebo-controlled study, enrolled 182 adults with rCDI. Results published in The New England Journal of Medicine in January 2022 showed that 88% of subjects in the Vowst group were free from C. difficile recurrence at eight weeks post-treatment, compared to 60% in the placebo group. At 24 weeks, 79% of the Vowst group were still free from the infection’s return, compared to 53% in the placebo group, reinforcing the durable relief. The drug proved well tolerated, with no drug-related serious adverse events.

Ecospor IV was an open-label extension of ECOSPOR III and open-label program for evaluating Vowst in 263 adults with rCDI at the commercial dose, carried out in order to fulfill FDA requirements for the safety database. The study duration for both cohorts was about 27 weeks, including a three-week screening period, an eight-week primary efficacy period and a 16-week follow-up period. Topline results indicated that the safety profile was well-tolerated and there was a 91% sustained clinical response at eight weeks in the overall population. At 24 weeks post-treatment, 86% of subjects treated with SER-109 experienced sustained clinical response.

In July 2021, Cambridge, Mass.-based Seres signed an agreement with Nestlé Health Science SA, of Lutry, Switzerland, to jointly commercialize Vowst in the U.S. and potentially Canada. Terms called for Nestlé to deploy its global pharmaceutical business, Aimmune Therapeutics UK Ltd., of London, and serve as lead commercialization party. Seres banked an up-front license payment of $175 million and was in line to collect $125 million upon FDA approval of Vowst. The agreement also includes sales target milestones which, if achieved, would total up to $225 million. Seres is paying development and pre-commercialization costs in the U.S. Upon commercialization, the firm will be entitled to 50% of profits.

“Don’t short this launch,” advised Oppenheimer analyst Mark Breidenbach urged investors ahead of the FDA go-ahead for Vowst. “We believe initial marketing efforts will focus on outpatient [gastrointestinal (GI) care] providers, supported by Nestlé’s established GI-focused field force and commercial infrastructure,” he wrote in a March 7 report. “Our discussions with GI docs who treat rCDI point to awareness of and enthusiasm for [Vo, thanks in part to high-profile publications of clinical data supporting its BLA – setting the stage for robust commercial uptake, assuming no major hiccups with securing payer coverage.” Breidenbach reiterate his “outperform” rating on Seres shares (NASDAQ:MCRB), with a $12 price target. The stock has reached a 52-week high of $9.49 and a low of $2.50.

Seres CEO Eric Shaff said during the company’s March call on fourth-quarter 2022 financials that “we've been working on this process for some time” and officials are “pleased to be taking our phase III process to launch,” with “a number of different launch scenarios” eyed. “We're really pleased with where we are, and we expect to be well prepared for the approval and then for launch thereafter.” David Ege, chief technology officer, said the phase III manufacturing process “is adequate in scale and volume to meet the near-term forecast that we have, together with Nestlé. By design, Bacthera [AG, of Basel, Switzerland] will start producing material ahead of the facility approval in 2024, and we anticipate an approval for that material to reach the market in 2025.”

Seres has had setbacks. In the summer of 2021, topline results from the phase IIb study called Eco-Reset with SER-287, made of a consortium of cultivated bacteria, missed its endpoint in patients with mild to moderate ulcerative colitis. The road for Vowst has not been entirely smooth, either, and includes a July 2016 phase II endpoint miss in rCDI.

The competitive space includes such players as Cambridge, Mass.-based Vedanta Biosciences Inc., which April 25 raised $106.5 million to support pivotal-stage development of its lead candidate, VE-303 for the prevention of rCDI and a phase II study with VE-202 for ulcerative colitis, among other development activities. The VE-303 study would be the first pivotal phase III trial with a therapeutic candidate based on a defined bacterial consortium, which Vedanta is developing as a next-generation approach to microbiome therapy. Defined bacterial consortia, since they are products of standardized composition made from cell banks, allow for bypassing reliance on inconsistently composed donor fecal material, the company said. In January 2023, Somerville, Mass.-based Finch Therapeutics Group Inc. sidelined its rCDI prospect, an oral microbiota drug known as CP-101, and laid off 95% of the workforce. Specifically, Finch chose to discontinue the Prism4 phase III trial due to slower-than-anticipated enrollment and the inability to secure capital or partnerships to help fund the program, along with broader sector trends, plus what Finch said was “the harmful impact of ongoing unauthorized use of the company’s intellectual property.”

The IP reference likely refers to Finch’s ongoing legal battle that began when Rebiotix Inc., of Roseville, Minn., and Ferring Pharmaceuticals Inc., of Saint-Prex, Switzerland, sought a declaratory judgment in December 2021 of non-infringement and invalidity of seven U.S. patents held by Finch. Rebiotix and Ferring gained U.S. FDA approval in November 2022 of Rebyota (fecal microbiota, live-jslm) for rCDI. Finch, along with the University of Minnesota, filed counterclaims of patent infringement.

Seres’ stock was at $6.88, up $0.48 in premarket trading on Thursday.