RBX2660 & Clostridioides difficile infection (CDI) (recurrent)

RBX2660 has received FDA approval in the United States for the prevention of Clostridioides difficile infection (CDI) (recurrent) in adults following antibiotic treatment for rCDI. This marks RBX2660 as the first rectally administered microbiota-based live biotherapeutic product approved by the FDA specifically for this indication. Multiple systematic reviews and meta-analyses, as well as clinical studies, confirm its effectiveness in reducing the risk of CDI recurrence in adult populations (1, 2, 3)

It is administered via enema (4)

RBX2660, a live biotherapeutic product offers a very promising treatment option for patients with Clostridioides difficile infection (CDI) (recurrent). RBX2660 restores the healthy gut microbiome and shows clinically meaningful benefits for patients suffering from Clostridioides difficile infection (CDI) (recurrent) (5)

Randomized clinical trials (RCTs)

NCT02299570
the clinical trial did not achieve its pre-defined primary goal of treatment success at 8 weeks following two doses of RBX2660 compared to two doses of placebo. However, the trial yielded clinically significant data that supported moving forward with a single dose regimen in the phase 3 clinical trial, PUNCH CD3, which has now been completed (6).

NCT03244644
demonstrated both safety and effectiveness in reducing recurrent Clostridioides difficile infection (CDI). This outcome is achieved after the administration of standard-of-care antibiotics, with the beneficial effects of the treatment lasting for up to six months (7)

Non-randomized clinical trials

NCT01925417
revealed that RBX2660 via enema is safe and effective for recurrent or severe CDI (11).

NCT03931941
subgroup analysis of PUNCH CD3-OLS suggests RBX2660 is safe and efficacious in patients with IBD and Clostridioides difficile infection (CDI) (recurrent) (8).It is effective for preventing rCDI in participants who have mild to moderate immunocompromising conditions (9)

NCT02589847
demonstrated safety and effectiveness in reducing the recurrence of rCDI when compared to a historical control group. The changes observed in the microbiome align with restorative alterations that are associated with resisting the recurrence of C. difficile (10)

References

(1) Doosetty et al. 2024 Cureus 16(4): e58862
(2) DuPont et al. 2024 Therap Adv Gastroenterol 17: 17562848241253089
(3) Feuerstadt et al. 2024 J Clin Gastroenterol 58(8): 818-824
(4) Stallhofer et al. 2024 Visc Med 40(2): 82-91
(5) Chopra 2023 Expert Review of Anti-Infective Therapy 21(3): 243-253
(6) Dubberke et al. 2023 Infect Dis Ther 12: 703-709
(7) Khanna et al. 2022 Drugs 82: 15271538
(8) Allegretti et al. 2025 Inflammatory Bowel Diseases 31(8): 2112-2122
(9) Alonso et al. 2025 Open Forum Infect Dis 12(4): ofaf117
(10) Orenstein et al. 2022 BMC Infect Dis 22(1): 245
(11) Orenstein et al. 2016 Clin Infect Dis 62(5): 596-602

see also:
Clostridioides difficile infection (CDI) (recurrent) & Drugs/Treatments
Microbiome-based therapeutics & Clostridioides difficile infection (CDI) (recurrent)