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RBX2660 safe, efficacious for recurrent C. difficile prevention
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WASHINGTON — The investigational microbiota-based drug, RBX2660, safely and effectively prevented recurrent Clostridioides difficile infection, or rCDI, and demonstrated clinical durability 2 years after treatment, according to findings from the PUNCH open-label study presented at IDWeek.
“C. difficile infections are a significant problem worldwide, primarily with respect to recurrence and the ongoing propagation of recurrence,” Ken Blount, PhD, chief scientific officer of Ferring Pharmaceuticals-owned Rebiotix, said in a presentation. “As it is also becoming very clear, microbiota restoration is needed for this indication to prevent recurrence.”
RBX2660 is a nonantibiotic, broad-spectrum microbiota suspension that is delivered directly to the intestinal tract via an enema. In 2016, the investigational drug was shown to safely prevent rCDI among patients who had received a standard course of CDI antibiotics. This was followed by a trial in 2017 that demonstrated RBX2660 met the primary endpoint of preventing a recurrence of CDI through week 8.
The findings presented this week at the conference comprised the final 24-month analysis of RBX2660’s clinical safety, efficacy and microbiome restoration.
Patients with multi-recurrent CDI were included in the phase 2, multicenter, open-label study and received two doses of RBX2660 7 days apart. To determine its efficacy, the researchers looked for the absence of CDI recurrence through 56 days after the last dose. This was then compared with the 8-week recurrence-free rates for an historical control cohort that received a standard-of-care antibiotic course. The regimen’s durability was determined by sustained absence of CDI episodes beyond 8 weeks. The researchers assessed its safety and durability at 3, 6, 12 and 24 months, according to the abstract.
“We generally saw a similar safety profile between the RBX2660-administered group and the control group,” Blount noted in his presentation.
At 8 weeks, RBX2660 was 79% effective for the prevention of rCDI compared with 31% in the historical control group. The researchers noted that efficacy was not impacted by patients’ age or sex.
Blount reported that 95 patients were evaluable for long-term durability because they achieved treatment success at 8 weeks. Among this population, eight had a new CDI episode by the 24-month follow-up, resulting in an overall durability of 91% for RBX2660.
“Twenty-four months is a long time,” Blount said. “Our first patient was enrolled in 2015, so we’re happy to have this final data.”
The researchers also investigated microbiome changes. They analyzed 503 stool samples collected from 110 treatment responders and discovered that the relative abundance of Bacteroidia and Clostridia remained higher than pre-treatment levels within 7 days of treatment. Moreover, the abundance of Gammaproteobacteria and Bacilli sharply declined following treatment. The researchers said these microbiome changes persisted for at least 24 months. During his presentation, Blount said that this represented a “significant and durable microbiota shift.” – by Marley Ghizzone
References:
Orenstein R, et al. Abstract LB5. Presented at: IDWeek; Oct. 2-6, 2019; Washington.
Rebiotix. Frequently Asked Questions. https://www.rebiotix.com/news-media/rebiotix-faqs. Accessed October 2, 2019.
Disclosure: Blount is the chief scientific officer for Rebiotix Inc.