4D pharma Presents Additional Positive Results of Phase II Study of Blautix® for the Treatment of Irritable Bowel Syndrome
4D pharma (NASDAQ: LBPS) announced positive data from its Phase II trial of LBP Blautix® for treating irritable bowel syndrome (IBS) with constipation (IBS-C) and diarrhea (IBS-D). The study revealed strong efficacy signals, particularly in the US, despite a high placebo response in UK and Ireland patients. Blautix, the first single-strain therapeutic for IBS-C and IBS-D, demonstrated significant improvements in bowel habits and abdominal pain. The company plans further regulatory discussions following these encouraging findings.
- Statistically significant improvement in bowel habit for IBS-D (62.0% vs placebo 47.4%, p=0.042).
- Clinically meaningful response rates in both IBS-C and IBS-D, supporting larger studies.
- Blautix showed a more than two-fold greater overall response rate in US IBS-D patients (29.3% vs placebo 14.3%, p=0.07).
- No severe treatment-related adverse events reported, with a safety profile comparable to placebo.
- High placebo response in the UK and Ireland impacted topline results.
- Placebo response rates were higher for IBS-C and IBS-D in UK and Ireland, raising concerns about efficacy.
4D pharma plc (AIM: DDDD; NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs) - a novel class of drug derived from the microbiome, today announces additional positive data from its completed Phase II trial of LBP Blautix® in subjects with irritable bowel syndrome with constipation (IBS-C) or with diarrhea (IBS-D).
The data has been presented in a poster session at Digestive Disease Week (DDW), on May 22, 2021, by Professor Eamonn Quigley, M.D., Head of Gastroenterology and Hepatology at Houston Methodist Hospital, Professor of Medicine at Weill Cornell Medical, and Chief Investigator of the study.
4D pharma previously announced topline efficacy and safety results from the trial, conducted in the US, UK and Ireland, in October 2020. Further analysis of the data has revealed strong and statistically significant activity on the key symptom of bowel habit, a potential approvable primary endpoint per regulatory guidelines. In addition, analysis of the data by geographical region shows that earlier topline results were impacted by an unusually high placebo response in patients in the UK and Ireland, and enhanced positive signals were seen in the larger US population.
Single strain LBP Blautix is the first therapeutic globally to have demonstrated efficacy in both IBS-C and IBS-D. The clinically meaningful overall response rates and improvements in bowel habit in both IBS-C and IBS-D in this signal finding Phase II trial, in spite of an unexpectedly high placebo response in certain patient groups, are highly encouraging for subsequent larger studies with increased statistical power.
“Following the announcement of the topline results in October, 4D pharma has been able to review the data in more detail. We have also discussed the results with internationally renowned key opinion leaders and patient groups. We are encouraged by the positive outcomes of this additional analysis, and we strongly believe that this signal finding study supports the continued development of Blautix as a novel treatment for IBS,” said Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma. “The Phase II results, in conjunction with regulatory guidance and KOL discussions, provide a clear and viable path forward for 4D pharma to continue to develop Blautix to address a significant unmet need. Topline results were significantly impacted by an unusually high placebo response in certain geographical patient groups. Despite this, the activity of Blautix relative to placebo in this Phase II study is competitive with approved IBS therapeutics. We are pleased to now share our additional positive findings following more detailed analysis of the clinical data. With the vital learnings we have gained, we are now even more enthusiastic about the chances of success in subsequent, larger, well-powered studies.”
“The idea of a single, safe, effective therapeutic able to address multiple sub-types of IBS is a hugely exciting proposition for both patients and clinicians. The level of efficacy achieved by Blautix in IBS-C and IBS-D is very encouraging for larger pivotal studies,” said Professor Eamonn Quigley, Chief Investigator of the study. “Importantly, the Phase II study used robust enrolment criteria and endpoints, setting the program up well for any pivotal studies. The efficacy and clean safety profile of Blautix presents an attractive package and a competitive position compared to what is currently available to prescribe to IBS patients.”
The signal finding Phase II study was a multi-centre, randomised, double-blind, placebo-controlled study. It enrolled 353 patients in the US, UK and Ireland with IBS-C or IBS-D as defined by the Rome IV criteria, and moderate or severe IBS symptom severity score (IBS-SSS) of ≥175 at screening (158 IBS-C and 195 IBS-D patients). Each sub-type cohort was randomized 1:1 to receive oral Blautix or placebo, two capsules twice daily, for 8 weeks. The study was designed to generate signals of activity in both IBS-C and IBS-D and to define key parameters for a pivotal program.
The previously announced overall responder rate (ORR) primary endpoint was assessed in all randomized subjects (N=353). ORR was also assessed in all patients evaluable for efficacy at eight weeks (N=316). Bowel habit and abdominal pain, the two components of the overall responder endpoint, were also analyzed independently. Post-hoc analyses of efficacy readouts by geographic region and gender subsets were also conducted.
Additional Efficacy Data
In the post-hoc sub-group analysis, in evaluable patients (IBS-C, N=147; IBS-D N=169), Blautix demonstrated the following:
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Statistically significant improvements in bowel habit in IBS-D (Blautix
62.0% vs placebo47.4% , p=0.042), and a strong effect nearing significance in IBS-C (Blautix53.8% vs placebo39.3% , p=0.054) in patients across all geographic regions. - Consistent improvements in bowel habit in patients receiving Blautix between geographic regions.
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An enhanced effect size in US patients due to a lower placebo response, achieving a statistically significant improvement in bowel habit in both IBS-C (Blautix
62.3% vs placebo42.6% , p=0.028) and IBS-D (Blautix®53.7% vs28.6% , p=0.014). -
Patients receiving Blautix reported progressive decreases in abdominal pain intensity over the treatment period. After eight weeks of treatment, evaluable IBS-C and IBS-D patients receiving Blautix reported an average decrease from baseline in weekly abdominal pain scores of
29.7% and34.4% , respectively. - Analysis of ORR by geographic region demonstrated comparable response rates in patients receiving Blautix regardless of region. This analysis did, however, identify a markedly greater placebo response in patients enrolled in the UK and Ireland compared to those enrolled in the US.
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In evaluable US patients, Blautix demonstrated a more than two-fold greater ORR than placebo in IBS-D (Blautix
29.3% vs placebo14.3% , p=0.07), and a clinically meaningful73% improvement in ORR over placebo in IBS-C (Blautix28.3% vs placebo16.4% , p=0.096). -
Placebo response rates were notably higher in UK and Ireland patients with IBS-C (Blautix
22.2% vs placebo20.0% , p=0.5) and IBS-D (Blautix25.6% vs placebo27.5% , p=0.5). -
A particularly strong, statistically significant overall response rate was observed in female IBS-D subjects across all regions (Blautix
34.6% vs placebo19.0% , p=0.05). This effect was enhanced and highly significant in US female IBS-D subjects (Blautix37.9% vs placebo9.4% , p=0.01).
Subjects in all regions met the same enrolment criteria, and there were no notable differences in baseline characteristics between regions. The Company has discussed the high placebo response in UK and Ireland patients with international key opinion leaders (KOLs) and IBS patient advocate groups, and identified a number of potential factors relating to placebo response and unrelated to study drug effectiveness in different populations.
Safety Data
As previously reported, Blautix demonstrated a safety profile comparable to placebo, with no treatment-related severe adverse events or serious adverse events. The most common adverse events were mild or moderate in severity, and were limited to (IBS-C and IBS-D cohorts combined) upper respiratory tract infection (
The Company continues to evaluate the Blautix Phase II data and plans to engage in regulatory discussions in the second half of 2021.
