dm+d

Unassigned

New Medicines

Clostridium difficile infection - prevention of recurrence

Information

Bacterial replacement
Nestle Health Science
Seres Therapeutics

Development and Regulatory status

None
None
Pre-registration (Filed)
Oct 22FDA accepts for review a Biologics License Application (BLA) for SER-109 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 PIII development programme, including ECOSPOR III (NCT03183128) and ECOSPOR IV (NCT03183141). Additionally, the BLA has been granted Priority Review designation with a Prescription Drug User Fee Act (PDUFA) target date of 26th April 2023 [18].
Jun 22Data from the III ECOSPOR IV study will support rolling BLA submission in the US. [16,17]
Jan 22Seres Therapeutics plan for BLA filing in mid-2022 with US FDA. They have partnered with Nestlé Health Science for markets outside of North America. [14]
Aug 20Seres Therapeutics plan talks with the FDA following positive data from the PIII ECOSPOR study.[11]
Apr 16Seres has announced that SER109 will move into PIII trials this year, although no further information is available; the company has an agreement with Nestle Health Sciences to market SER109 and related products outside the US and Canada [1].

Category

Bacteria replacement. An oral capsule containing spores from bacteria isolated from stool samples.
PHS England reports indicate an overall C. diff infection rate in English hospital Trusts of 41 per 100,000 bed days (14,165 reports) for FY 2014-15; total CCG attributed rate for specimens for the same year was 26.3 per 100,000 [2].
Clostridium difficile infection - prevention of recurrence
Oral

Trial or other data

Jun 22Topline results of PIII ECOSPOR IV study announced with positive results and a good safety profile.[16]
Jan 22Results of PIII ECOSPOR III study reported in NEJM [13]
Oct 21SERES present additional data from PIII ECOSPOR III study (n=182) at conference; SER-109 reduced risk of rCDI vs. placebo in patients with risk factors for recurrence, including those taking acid suppressants (40.7% of patients). Seres plan to submit a BLA mid-2022 [12].
Aug 20SER-109 met the primary endpoint in the PIII ECOSPOR study with a significantly lower recurrence rate of 11.1% in SER-109 pts vs. 41.3% with placebo at 8 weeks (30% lower rate of recurrence with SER-109, p=0.001). Safety results were considered favorable and similar to placebo, mainly being flatulence, abdominal distention and abdominal pain which was generally mild to moderate in nature.[11]
May 20The PIII ECOSPOR III (NCT03183128) and its open-label extension ECOSPOR IV (NCT03183141) are still recruiting, with an estimated primary completion date of Jul 2020, and Feb 2020, respectively [10].
Dec 18The PIII ECOSPOR III (NCT03183128) and its open-label extension ECOSPOR IV (NCT03183141) are still recruiting, with an estimated primary completion date of Feb 2019, and April 2019, respectively [6].
Jun 17The ECOSPOR III study has commenced and has been designated PIII by the US FDA. Recruitment is underway in the US (NCT03183128) [7,8].
Mar 17Seres announces plans to initiate a new SER-109 PII study (ECOSPOR III) in patients with multiply recurrent C. difficile infection. The ECOSPOR III study design was finalized following a positive Type B meeting with the FDA. 320 patients with multiply recurrent C. difficile infection will be randomized 1:1 between SER-109 and placebo. To ensure accurate measurement of C. difficile infection, diagnosis of recurrent C. difficile infection for both study entry and for endpoint analysis will be confirmed by C. difficile cytotoxin assay. Patients in the SER-109 arm will receive a total SER-109 dose, administered over three days, approximately 10-fold higher than the dose used in the prior ECOSPOR study. ECOSPOR III will evaluate patients for 24 weeks and the primary endpoint will compare the C. difficile recurrence rate in subjects who receive SER-109 verses placebo at up to eight weeks after dosing. The FDA has agreed that this new trial may qualify as a pivotal study with achievement of a persuasive clinical effect and addressing FDA requirements, including clinical and statistical factors, an adequately sized safety database, and certain CMC parameters [6].
Jul 16Seres Therapeutics announces that in a PII trial, SER-109 failed to outperform a placebo in terms of cutting the risk of Clostridium difficile infection (CDI). The PII study enrolled 89 subjects and randomized them to receive either SER-109 or a placebo. Once the subjects completed antibiotic treatment for CDI, two-thirds of them received a single oral dose of the bacterial spores that make up SER-109, with the remaining one-third getting a placebo. At 8 weeks, 44% of participants experience a recurrence of CDI. A little more than half of subjects who received the placebo saw their CDI recur; this difference fell short of being a statistically significant reduction in relative risk of CDI recurrence, leaving the firm with a Phase II trial that failed to meet its primary endpoint. Among subjects aged under 65 years old, placebo bested SER-109. The next step for Seres is to compare the PII data to results generated in an earlier investigator sponsored PIb trial. Once Seres has a handle on the situation, it plans to talk with FDA and revise its development strategy as required [5].
Feb 16Positive results of a phase Ib/II study published in J Infect Dis (PubMed ID 26908752) - 26 of 30 enrolled patients met the primary efficacy outcome of absence of C. diff diarrhoea during 8-week follow-up [3].
May 15Multicentre, randomised, placebo-controlled trial initiated (NCT02437487) in the US; estimated recruitment 87, primary outcome is absence of clinically-significant CDI at eight weeks and estimated completion date Mar 16 [4].