Summit Therapeutics Presents Additional Data From Phase 1b Modified Diet Clinical Trial of SMT C1100 in DMD Patients at WMS
30 September 2015 - 9:00PM
- 10 of 12 Patients Achieved Plasma Concentrations
Expected to Increase Utrophin Levels by Approximately 30% or
Greater
- Phase 2 Proof of Concept Trial Design Outlined,
Expected to Initiate Q4 2015
- Preclinical Presentations Support Utrophin Modulation
as Potential Treatment for all Patients with DMD
Summit Therapeutics plc (NASDAQ:SMMT) (AIM:SUMM), the drug
discovery and development company advancing therapies for Duchenne
muscular dystrophy ('DMD') and Clostridium difficile infection,
will today present detailed pharmacokinetic data from the Phase 1b
modified diet clinical trial of SMT C1100 for the treatment of DMD,
as well as preclinical data supporting both SMT C1100 and the
broader utrophin modulator pipeline, at the 20th International
Congress of the World Muscle Society ('WMS'). SMT C1100 is a
utrophin modulator that the Company believes has potential to treat
all patients with DMD.
"We believe utrophin modulation has significant potential as a
universal treatment for DMD. For example, in preclinical studies,
continual production of utrophin has resulted in disease-modifying
effects in DMD models. Those preclinical findings, together with
the detailed pharmacokinetic data from this recent trial, further
our belief that SMT C1100 could have clinical benefit across all
patients with DMD," said Ralf Rosskamp, MD, Chief Medical
Officer of Summit. "We are thrilled to have the
opportunity to provide hope for the patients and families living
with this devastating disease, and look forward to initiating a
Phase 2 trial, which aims to provide proof of concept for SMT C1100
through measurements of muscle health and function, in the fourth
quarter of this year."
As previously reported, the Phase 1b modified diet trial met its
primary objective. In this trial, increases in plasma absorption of
SMT C1100 were observed in DMD patients who received SMT C1100
while following specific dietary guidance providing for a balanced
diet of fats, proteins and carbohydrates. In the detailed
pharmacokinetic data to be presented at WMS, ten of 12 patients
achieved plasma exposure levels above 30 ng/ml for a mean of 14
hours in a 22-hour period, and six of those patients achieved
plasma exposure levels above 67 ng/ml for a mean of 8.2 hours in
the 22-hour period. These plasma levels correlate to an in vitro
increase in utrophin levels of approximately 30% and 50%,
respectively, in DMD myoblast cells and human myotubes. Since
sustaining utrophin production is likely to be key in providing
therapeutic benefit, the remaining two patients may also achieve
some clinical benefit as they had plasma levels that exceeded 20
ng/ml. Summit's upcoming Phase 2 proof of concept trial will
evaluate the potential benefit of SMT C1100 with longer-term
dosing. Based on the detailed analysis of the Phase 1b modified
diet trial, drug plasma exposure will not be used as an entry
criterion for the Phase 2 proof of concept trial.
Summit plans to initiate its Phase 2 proof of concept trial of
SMT C1100 in patients with DMD in the fourth quarter of this year.
The 48-week open-label study is expected to enroll up to 40
patients between the ages of five and 10 years old at sites in
Europe and in the US. Planned endpoints are expected to include
changes in the fat content of muscle and in muscle inflammation as
measured by magnetic resonance imaging ('MRI') of the leg muscles,
measurements of utrophin protein and muscle fibre regeneration from
muscle biopsies, and functional measures such as the six minute
walk test and the North Star Ambulatory Assessment. The Company
expects to report data from this trial periodically over the course
of the study. The design and initiation of this study remain
subject to regulatory approval. In addition, Summit continues to
evaluate the timing and design for a larger, placebo-controlled
trial of SMT C1100.
Additional Highlights from the WMS
Presentations
SMT C1100 Clinical Development – Phase 1b Modified Diet
Clinical Trial
- Seven of the 12 patients had higher plasma exposure of SMT
C1100 after Day 14 compared to Day 1, which was not observed in
previous studies of this drug.
- Six of the seven patients who had also participated in a
previous Phase 1b study had increased plasma exposures of SMT C1100
in the modified diet trial ranging from 50% to nearly 400% with the
modified diet compared to the previous trial; the seventh patient
had plasma concentrations that exceeded 130 ng/ml for the entire
final day of dosing in both Phase 1b trials.
- SMT C1100 was well-tolerated in all patients with no severe or
serious adverse events and no discontinuations due to an adverse
event.
- Patient compliance was 100%.
Biomarker Development Programme
- Presentation on biomarker development to automate the
quantification of muscle fibre regeneration in muscle biopsies from
patients with DMD and Becker muscular dystrophy ('BMD').
- Results show the ability to detect reduced rates of fibre
regeneration in an automated fashion, potentially removing the
uncertainty of manual grading of the muscle fibres. This was shown
through an excellent correlation in fibres predicted to have lower
fibre regeneration in BMD patients compared to dystrophin deficient
DMD biopsies.
- Aim is to provide an automated technique for use in future
utrophin modulator clinical trials.
Second Generation Utrophin Modulator Pipeline
Development
- Preclinical data from the in vivo mdx mouse disease model
showing that second generation utrophin modulators increase
utrophin protein levels along the entire length of a muscle fibre
and that this results in significantly improved muscle stability
and reduction in levels of muscle fibre regeneration, necrosis and
fibrosis.
- Second generation modulators show increased utrophin expression
in the diaphragm and protection against muscle fibre damage and
fibrosis in the mdx mouse disease model. This is a significant
observation due to the disease pathology in the diaphragm of the
mdx model closely resembling that of DMD patients.
- Data set supports the potential of utrophin modulation as a
mechanism to treat DMD that is independent of the underlying
genetic fault.
Copies of the posters are now available from the 'Programmes'
section of Summit's website, www.summitplc.com.
About the Phase 1b Modified Diet Trial
The Phase 1b randomised, placebo controlled clinical trial was
designed to evaluate the blood plasma levels of SMT C1100 in
paediatric patients with DMD. Patients and their caregivers were
provided with specific dietary guidance on recommended balanced
proportions of fats, proteins and carbohydrates. The trial enrolled
a total of 12 patients aged between 5 and 13 years, divided equally
into three dose cohorts, at trial sites in the UK. Patients were
randomised to three groups over 14-day treatment periods during
which each patient received two different doses of SMT C1100 and a
placebo control. There was a washout period of at least 14 days in
between each of the treatment periods.
About Utrophin Modulation in DMD
DMD is a progressive muscle wasting disease that affects around
50,000 boys in the developed world. The disease is caused by
different genetic faults in the gene that encodes dystrophin, a
protein that is essential for the healthy function of all muscles.
There is currently no cure for DMD and life expectancy is into the
late twenties. Utrophin protein is functionally and structurally
similar to dystrophin. In preclinical studies, the continued
expression of utrophin has a meaningful, positive effect on muscle
performance. Utrophin modulation has the potential to slow down or
even stop the progression of DMD, regardless of the underlying
dystrophin mutation. It is also expected that utrophin modulation
could potentially be complementary to other therapeutic approaches
for DMD.
About Summit Therapeutics
Summit is a biopharmaceutical company focused on the discovery,
development and commercialisation of novel medicines for
indications for which there are no existing or only inadequate
therapies. Summit is conducting clinical programs focused on the
genetic disease Duchenne muscular dystrophy and the infectious
disease C. difficile infection. Further information is available at
www.summitplc.com and Summit can be followed on Twitter
(@summitplc).
For more information, please contact:
Summit |
|
Glyn Edwards / Richard Pye
(UK office) |
Tel: +44 (0)1235 443 951 |
Erik Ostrowski / Michelle Avery (US
office) |
+1 617 225 4455 |
|
|
Cairn Financial Advisers
LLP |
|
(Nominated Adviser) |
|
Liam Murray / Tony Rawlinson |
Tel: +44 (0)20 77148 7900 |
|
|
N+1 Singer |
|
(Broker) |
|
Aubrey Powell / Jen Boorer |
Tel: +44 (0)20 7496 3000 |
|
|
Peckwater PR |
|
(Financial public relations, UK) |
Tel: +44 (0)7879 458 364 |
Tarquin Edwards |
tarquin.edwards@peckwaterpr.co.uk |
|
|
MacDougall Biomedical
Communications |
|
(US media contact) |
Tel: +1 781 235 3060 |
Chris Erdman |
cerdman@macbiocom.com |
Forward-looking Statements
Any statements in this press release about Summit's future
expectations, plans and prospects, including but not limited to,
statements about the clinical and preclinical development of
Summit's product candidates, the therapeutic potential of Summit's
product candidates, and the timing of initiation, completion and
availability of data from clinical trials, and other statements
containing the words "anticipate," "believe," "continue," "could,"
"estimate," "expect," "intend," "may," "plan," "potential,"
"predict," "project," "should," "target," "would," and similar
expressions, constitute forward looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by such
forward-looking statements as a result of various important
factors, including: the uncertainties inherent in the initiation of
future clinical trials, availability and timing of data from
on-going and future clinical trials and the results of such trials,
whether preliminary results from a clinical trial will be
predictive of the final results of that trial or whether results of
early clinical trials or preclinical studies will be indicative of
the results of later clinical trials, expectations for regulatory
approvals, availability of funding sufficient for Summit's
foreseeable and unforeseeable operating expenses and capital
expenditure requirements and other factors discussed in the "Risk
Factors" section of filings that Summit makes with the Securities
and Exchange Commission including Summit's Annual Report on Form
20-F for the fiscal year ended January 31, 2015. Accordingly
readers should not place undue reliance on forward looking
statements or information. In addition, any forward looking
statements included in this press release represent Summit's views
only as of the date of this release and should not be relied upon
as representing Summit's views as of any subsequent date. Summit
specifically disclaims any obligation to update any forward-looking
statements included in this press release.
-END-
Summit Therapeutics (NASDAQ:SMMT)
Historical Stock Chart
From Jun 2024 to Jul 2024
Summit Therapeutics (NASDAQ:SMMT)
Historical Stock Chart
From Jul 2023 to Jul 2024