TIDMDDDD
RNS Number : 3004B
4d Pharma PLC
07 October 2020
4D pharma announces topline results from Blautix(R) Phase II
trial in irritable bowel syndrome (IBS)
Positive trends seen in primary efficacy endpoint of the study
of overall response in both IBS-C and IBS-D subgroups
Statistically significant impact on overall response in combined
IBS-C and IBS-D group
Blautix(R) was well tolerated, with a safety profile comparable
to placebo
Phase II trial results provide strong foundation for the
continued development of the first therapeutic with potential to
treat both major subtypes of IBS
Leeds, UK - October 7, 2020 - 4D pharma plc (AIM: DDDD), a
pharmaceutical company leading the development of Live
Biotherapeutics, today announces encouraging topline results from
its Phase II BHT-II-002 trial of Blautix(R), a single strain Live
Biotherapeutic to treat irritable bowel syndrome (IBS).
Consistent with FDA guidance on the clinical evaluation of
treatments for IBS, 4D pharma plc ('4D') investigated the effect of
Blautix(R) on both bowel habit and pain as a composite response
endpoint. 4D pharma also investigated the treatment across both
IBS-C (constipation predominant) and IBS-D (diarrhoea predominant)
clinical subtypes, as Blautix(R) has potential to treat both major
subtypes of the disease, unlike other approved products which act
only on symptoms associated with either subtype of IBS.
The Phase II trial showed that Blautix(R) treatment resulted
in:
-- A statistically significant increase in overall response in
pre-planned analysis of the combined IBS-C/D group compared to
placebo;
-- A positive, though non-significant, increase in overall
response in both IBS-C and IBS-D cohorts;
-- Safety profile of Blautix(R) was comparable to placebo,
contrasting with many existing therapies which have significant
side effect profiles limiting their utility; and
-- Positive data trends in population sub-groups within both
disease subtypes that warrant further analysis and
investigation.
The results of the study demonstrated that Blautix(R) has levels
of activity in both IBS-C and IBS-D that are comparable to other
drugs approved solely in either indication. The randomised Phase II
study was designed to generate data to guide the pivotal
development phase of the Blautix(R) program and the results shown
give the Company confidence and the necessary data for the design
of a Phase III pivotal programme.
The commercial opportunity provided by Blautix(R) could be
substantial, given the need for a safe and effective treatment
across IBS-C and IBS-D populations.
"IBS is a common and important condition that can have a
significant impact on patients' quality of life. The prospect of a
treatment that could equally benefit both IBS-C and IBS-D with a
strong safety profile is very compelling," said Prof. Eamonn
Quigley, Head of Gastroenterology and Hepatology at Houston
Methodist Hospital and the Study's Chief Investigator. "I am
impressed with the improvement in bowel habit that was observed for
Blautix in both IBS-C and IBS-D in the current trial, and believe
that it is deserving of further study as it could provide an
attractive treatment option in the future."
"We are very pleased with the outcome of the Blautix Phase II
study, demonstrating not only that Blautix has an effect in both
IBS-C and IBS-D, but that it has a favourable safety profile. This
is very relevant in a condition where all approved treatments only
have activity in either IBS-C or IBS-D, and many have
treatment-limiting side effects. Blautix could provide a highly
differentiated option for patients and physicians," said Dr. Alex
Stevenson, Chief Scientific Officer of 4D pharma.
"Uniquely for a single agent, th e Blautix Phase II study has
generated combined data across both sub-types of IBS. The effect
shown by Blautix across both sub-types indicates it may potentially
provide a solution to IBS-M patients whose symptoms fluctuate
between IBS-C and IBS-D. These patients, who account for around 30%
of all IBS patients, currently have no approved treatment options.
This reflects the broad potential of Blautix as a completely new,
safe, flexible therapeutic approach to treating all forms of the
condition. The Phase II results provide signals that are highly
encouraging and supportive of regulatory engagement around the
design of a Phase III pivotal study to provide new therapeutic
options to cover the considerable unmet medical need of people
suffering from IBS."
Blautix(R) Study Design and Results
The Blautix(R) Phase II study (ClinicalTrials.gov identifier:
NCT03721107) is a multicentre, randomised, placebo-controlled study
that enrolled a total of 353 patients with IBS-C or IBS-D with
eligible baseline data (158 and 195 patients respectively).
Patients in each cohort were randomised 1:1 to receive either
Blautix(R) or placebo; in total, 76 IBS-C patients and 94 IBS-D
patients received Blautix treatment. Blautix(R) or placebo was
administered orally as two capsules, twice daily for 8 weeks.
The primary efficacy endpoint of the trial was based on whether
or not a subject, from either the IBS-C or IBS-D cohorts, was
considered an overall responder. For a subject to be classed as an
'overall responder' they must have reported an improvement in their
weekly (cohort specific) symptoms (abdominal pain intensity and
stool frequency or consistency) for >=50% of the treatment
period. The primary efficacy endpoint was also investigated in the
combined IBS-C/D group as part of the planned analysis of the
study.
The randomised Phase II study was designed to generate data in
both IBS-C and IBS-D that could be used to guide the subsequent
pivotal development phase of Blautix(R). As such, statistical
testing of the primary efficacy endpoint was one-sided and
performed at the 0.10 significance level for each individual
cohort. No correction for multiple analyses was applied. The power
of the study to detect a difference vs placebo was based on a
placebo response rate of 40% and Blautix(R) response rate of 55%.
This represents a relative risk (RR) vs placebo of 1.37.
The primary efficacy endpoint was analysed in the Full Analysis
Set (FAS) of all randomised subjects, including those who had
protocol violations deemed to impact the assessment of
efficacy.
A summary of the results for the FAS (n=353) is given below,
showing Blautix(R) achieved:
-- In the IBS-C/D combined group (n=170), a statistically
significant overall response rate of 24.1% compared to 17.5% for
placebo (n=183) (p=0.0625), representing an RR of 1.38 (95%
confidence interval: 0.913, 2.083);
-- In IBS-C patients (n=76) a numerically superior but
statistically non-significant overall response rates of 25%
compared to 17.1% for placebo (n=82) (p=0.152), representing an RR
of 1.46 (95% confidence interval: 0.791, 2.711); and
-- In IBS-D patients (n=94) a numerically superior but
statistically non-significant overall response rate of 23.4%
compared to 17.8% for placebo (n=101) (p=0.216), representing an RR
of 1.31 (95% confidence interval: 0.753, 2.290).
The response rate was also assessed for those patients who
completed the 8-week treatment period without any major protocol
deviations, the Efficacy Evaluable Analysis Set (EEAS). The EEAS
typically represents the patient population with greatest level of
study compliance and better represents the effect of the treatment.
In the EEAS population, Blautix(R) treatment compared to placebo
demonstrated an increased statistically significant overall
response rate in the combined IBS-C/D group, a nominally
statistically significant effect in the IBS-C cohort, and an
increase in overall response rate in IBS-D.
Blautix(R) also showed a highly favourable safety profile, with
a total of 58 adverse events (AEs) in 177 (32.8%) subjects compared
to 68 AEs in 188 (33.0%) subjects receiving placebo. There was 1
serious adverse event (SAE) in the Blautix(R) treated (0.6%) and 1
SAE in the placebo treated group (0.5%). Neither SAE was deemed to
be treatment related.
The Company is currently undertaking further analysis of the
study results, including investigation of sub-groups with signals
of higher levels of overall response, in order to define the future
pivotal clinical development strategy.
A presentation describing the Phase II results in more detail
can be found on 4D pharma's website at
https://www.4dpharmaplc.com/en/investors/reports-presentations
.
About Blautix(R)
Blautix(R) is a single strain Live Biotherapeutic product (LBP),
being developed as a treatment for both IBS-C and IBS-D.
Pre-clinical studies demonstrated its ability to address visceral
hypersensitivity and other symptoms of IBS and increase microbiome
diversity. A Phase I study in healthy volunteers and IBS patients
showed that Blautix(R) was well tolerated and an improvement in
symptoms was also reported relative to placebo. The Phase II
BHT-II-002 trial demonstrated an impact on overall response with
regards to bowel habit and abdominal pain in IBS-C and IBS-D.
Blautix(R) was well tolerated, with a safety profile comparable to
placebo. Further information on the Phase II study can be found at
ClinicalTrials.gov Identifier: NCT03721107.
About IBS
Irritable bowel syndrome (IBS) has an incidence in the US of
10-15% of the population. IBS is clinically defined to different
subtypes - constipation-predominant (IBS-C), diarrhoea-predominant
(IBS-D) and mixed phenotype (IBS-M), which comprise in the US
38.5%, 32.5% and 29.0% of diagnosed cases respectively. Existing
approved treatments are focused on addressing the specific symptoms
of disease subtypes, rather than the underlying disease, and often
have only modest levels of efficacy and significant side effects.
Research indicates that the microbiome is altered in IBS patients
compared to healthy controls, but that the alteration is consistent
across the different subtypes, suggesting the possibility that a
microbiome-based intervention could address multiple subtypes.
About 4D pharma
Founded in February 2014, 4D pharma is a world leader in the
development of Live Biotherapeutics, a novel and emerging class of
drugs, defined by the FDA as biological products that contain a
live organism, such as a bacterium, that is applicable to the
prevention, treatment or cure of a disease. 4D has developed a
proprietary platform, MicroRx(R), that rationally identifies Live
Biotherapeutics based on a deep understanding of function and
mechanism.
4D's Live Biotherapeutic Products are orally delivered single
strains of bacteria that are naturally found in the healthy human
gut. The Company has six clinical studies in progress, namely a
Phase II clinical study of Blautix(R) in Irritable Bowel Syndrome
(IBS), a Phase I/II study of MRx0518 in combination with
KEYTRUDA(R) (pembrolizumab) in solid tumours, a Phase I study of
MRx0518 in a neoadjuvant setting for patients with solid tumours, a
Phase I study of MRx0518 in patients with pancreatic cancer, a
Phase I/II study of MRx-4DP0004 in asthma, and a Phase II study of
MRx-4DP0004 in patients hospitalised with COVID-19.
Preclinical-stage programs include candidates for CNS disease such
as Parkinson's disease and other neurodegenerative conditions. The
Company has a research collaboration with MSD, a tradename of Merck
& Co., Inc., Kenilworth, NJ, USA, to discover and develop Live
Biotherapeutics for vaccines.
For more information, refer to https://www.4dpharmaplc.com .
Contact Information:
4D
Duncan Peyton, Chief Executive Officer +44 (0)113 895 0130
Investor Relations ir@4dpharmaplc.com
N+1 Singer - Nominated Adviser and Joint Broker +44 (0)20 7496
3000
Aubrey Powell / Justin McKeegan / Iqra Amin (Corporate
Finance)
Tom Salvesen (Corporate Broking)
Bryan Garnier & Co. Limited - Joint Broker +44 (0)20 7332
2500
Dominic Wilson / Phil Walker
Image Box Communications
Neil Hunter / Michelle Boxall +44 (0)20 8943 4685
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