FDA accepts review of SeresTx BLA for oral microbiome therapeutic

Unlocking the gut microbiome’s secrets

The FDA has accepted for review Seres Therapeutics’ Biologics License Application (BLA) for SER-109, an investigational oral microbiome therapeutic for the prevention of recurrent Clostridium difficile infection (rCDI). If approved, SER-109 would be the first-ever FDA-approved oral microbiome therapeutic.

The BLA is supported by results from a completed phase 3 development programme, including ECOSPOR III (NCT03183128) and ECOSPOR IV (NCT03183141). Additionally, SeresTx’s BLA has been granted Priority Review designation with a Prescription Drug User Fee Act (PDUFA) target date of 26th April 2023.

In July 2021, Swiss food giant Nestle paid $175 million upfront for North American co-marketing rights to SER-109. If the oral therapeutic is approved by the FDA, Nestle’s Health Sciences unit will pay SeresTx another $125 million and line up a further possible $225 million in commercial milestones tied to sales targets. The two companies have been working together on this microbiome project since 2016.

There are some 170,000 cases of rCDI in the US each year and approximately 30,000 deaths. One of the three most urgent bacterial threats within the States, according to the Center for Disease Control (CDC) rCDI is a leading cause of hospital-acquired infection.

SER-109 is composed of purified Firmicutes spores designed to reduce recurrence of rCDI, and it has shown promise for improving the current standard of care. The phase 3 results from ECOSPOR III (SERES-012) were based on 182 adults with rCDI in a multicentre, randomised, placebo-controlled study and were published in the New England Journal of Medicine back in January this year. The study showed that at eight weeks post-treatment 88% of subjects in the SER-109 group were free from C. difficile recurrence, compared to 60% in the placebo group.

In the open-label extension study ECOSPOR IV (SERES-013), 263 adults with rCDI were evaluated when given a commercial dose of SER-109 to fulfil FDA requirements for the oral therapeutic’s safety database. Topline results indicated that SER-109 was well-tolerated and exhibited a 91% sustained clinical response eight weeks after treatment. At 24 weeks post-treatment, 86% of participants given SER-109 experienced a sustained clinical response.

Vice president of Medical Affairs at Seres Therapeutics, Dr Barbara McGovern, stated: “SER-109 is thought to restore host defences against C. difficile by increasing the diversity of the gut microbiome, thus reducing the risk of recurrence. [It] was also observed to reduce the abundance of Gram-negative bacteria – which carry ARGs – and these early observations are a promising avenue for further exploration, due to the urgent global need [to combat] antimicrobial drug resistance.”

Chief medical officer at the company, Dr Lisa von Moltke, said: “We’re aiming to strengthen the body’s defences against the return of C. difficile infection by repairing the microbiome. The clinical evidence to date from both [studies] continues to support the potential use of SER-109 to reduce the suffering and health risks inflicted by repeated occurrences of this incredibly difficult-to-treat disease.”

Since the announcement of the FDA’s acceptance for review of SeresTx’s BLA, the US microbiome therapeutics company’s shares have risen 18%. Now at $6.79 per share (Nasdaq: MCRB), in the last three months its stock has risen 62%.